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W B Van Den Berg - One of the best experts on this subject based on the ideXlab platform.
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alarmins s100a8 s100a9 aggravate Osteophyte formation in experimental osteoarthritis and predict Osteophyte progression in early human symptomatic osteoarthritis
Annals of the Rheumatic Diseases, 2016Co-Authors: R.f. Schelbergen, P M Van Der Kraan, W B Van Den Berg, W. De Munter, M.h. Van Den Bosch, F.p.j.g. Lafeber, Annet W. Sloetjes, Thomas Vogl, Johannes Roth, Arjen B. BlomAbstract:OBJECTIVE: Alarmins S100A8 and S100A9 are major products of activated macrophages regulating cartilage damage and synovial activation during murine and human osteoarthritis (OA). In the current study, we investigated whether S100A8 and S100A9 are involved in Osteophyte formation during experimental OA and whether S100A8/A9 predicts Osteophyte progression in early human OA. METHODS: OA was elicited in S100A9-/- mice in two experimental models that differ in degree of synovial activation. Osteophyte size, S100A8, S100A9 and VDIPEN neoepitope was measured histologically. Chondrogenesis was induced in murine mesenchymal stem cells in the presence of S100A8. Levels of S100A8/A9 were determined in plasma of early symptomatic OA participants of the Cohort Hip and Cohort Knee (CHECK) cohort study and Osteophytes measured after 2 and 5 years. RESULTS: Osteophyte size was drastically reduced in S100A9-/- mice in ligaments and at medial femur and tibia on days 21 and 42 of collagenase-induced OA, in which synovial activation is high. In contrast, Osteophyte size was not reduced in S100A9-/- mice during destabilised medial meniscus OA, in which synovial activation is scant. S100A8 increased expression and activation of matrix metalloproteinases during micromass chondrogenesis, thereby possibly increasing cartilage matrix remodelling allowing for larger Osteophytes. Interestingly, early symptomatic OA participants of the CHECK study with Osteophyte progression after 2 and 5 years had elevated S100A8/A9 plasma levels at baseline, while C-reactive protein, erythrocyte sedimentation rate and cartilage oligomeric matrix protein were not elevated at baseline. CONCLUSIONS: S100A8/A9 aggravate Osteophyte formation in experimental OA with high synovial activation and may be used to predict Osteophyte progression in early symptomatic human OA.
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Alarmins S100A8/S100A9 aggravate Osteophyte formation in experimental osteoarthritis and predict Osteophyte progression in early human symptomatic osteoarthritis
Annals of the Rheumatic Diseases, 2014Co-Authors: R.f. Schelbergen, P M Van Der Kraan, W B Van Den Berg, W. De Munter, M.h. Van Den Bosch, F.p.j.g. Lafeber, Annet W. Sloetjes, Thomas Vogl, Johannes Roth, Arjen B. BlomAbstract:OBJECTIVE: Alarmins S100A8 and S100A9 are major products of activated macrophages regulating cartilage damage and synovial activation during murine and human osteoarthritis (OA). In the current study, we investigated whether S100A8 and S100A9 are involved in Osteophyte formation during experimental OA and whether S100A8/A9 predicts Osteophyte progression in early human OA. METHODS: OA was elicited in S100A9-/- mice in two experimental models that differ in degree of synovial activation. Osteophyte size, S100A8, S100A9 and VDIPEN neoepitope was measured histologically. Chondrogenesis was induced in murine mesenchymal stem cells in the presence of S100A8. Levels of S100A8/A9 were determined in plasma of early symptomatic OA participants of the Cohort Hip and Cohort Knee (CHECK) cohort study and Osteophytes measured after 2 and 5 years. RESULTS: Osteophyte size was drastically reduced in S100A9-/- mice in ligaments and at medial femur and tibia on days 21 and 42 of collagenase-induced OA, in which synovial activation is high. In contrast, Osteophyte size was not reduced in S100A9-/- mice during destabilised medial meniscus OA, in which synovial activation is scant. S100A8 increased expression and activation of matrix metalloproteinases during micromass chondrogenesis, thereby possibly increasing cartilage matrix remodelling allowing for larger Osteophytes. Interestingly, early symptomatic OA participants of the CHECK study with Osteophyte progression after 2 and 5 years had elevated S100A8/A9 plasma levels at baseline, while C-reactive protein, erythrocyte sedimentation rate and cartilage oligomeric matrix protein were not elevated at baseline. CONCLUSIONS: S100A8/A9 aggravate Osteophyte formation in experimental OA with high synovial activation and may be used to predict Osteophyte progression in early symptomatic human OA.
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OP0146 Alarmins S100a8/S100a9 Aggravate Osteophyte Formation in Experimental Osteoarthritis and PREDICT Osteophyte Progression in Early Human Osteoarthritis in the Dutch CHECK Cohort
Annals of the Rheumatic Diseases, 2014Co-Authors: R.f. Schelbergen, P M Van Der Kraan, W B Van Den Berg, W. De Munter, M.h. Van Den Bosch, F.p.j.g. Lafeber, Annet W. Sloetjes, Thomas Vogl, Johannes Roth, Arjen B. BlomAbstract:Background The main pathological feature of osteoarthritis (OA) is degradation of the articular cartilage. Other important hallmarks include subclinical inflammation of the synovium and ectopic formation of new bone and cartilage at the ligaments or joint margins, termed Osteophytes. Alarmins S100A8 and S100A9 are major products of activated macrophages regulating cartilage damage and synovial activation during murine and human osteoarthritis (1) (OA). Objectives In the current study we investigated whether S100A8 and S100A9 are involved in Osteophyte formation during experimental OA and if S100A8/A9 predicts Osteophyte progression in early human OA. Methods OA was elicited in S100A9 -/- and wild-type C57Bl/6 mice in two experimental models that differ in degree of synovial activation. Osteophyte size, S100A8, S100A9 and VDIPEN expression was measured on histology. Chondrogenesis was induced in murine mesenchymal stem cells (MSCs) in the presence of S100A8. Levels of S100A8/A9 were determined in plasma of early symptomatic OA patients of the CHECK cohort study and Osteophyte size measured at baseline and after 2 and 5 years. Results S100A8 and S100A9 protein levels in the synovial lining and serum coincide with Osteophyte development in collagenase-induced OA (CIOA), in which synovial activation is high. Osteophyte size was drastically reduced in S100A9 -/- mice on day 21 and 42 of CIOA, in the medial collateral ligaments (58% and 93% reduction) and at medial femur and tibia (62% and 67% reduction). In contrast, Osteophyte size was not reduced in S100A9 -/- mice during destabilized medial meniscus OA, in which synovial activation is scant. One explanation for the reduced Osteophyte size in S100A9-/- mice may be a direct effect of S100-proteins on chondrogenesis. During in vitro chondrogenesis using murine MSCs, S100A8 caused a marked increase in MMP-3 mRNA and VDIPEN expression (as measure for MMP activity) as well as a strongly altered morphology, indicating increased remodeling allowing for larger Osteophytes. Interestingly, early symptomatic OA patients of the CHECK study with Osteophyte progression after two and five years had significantly elevated S100A8/A9 plasma levels at baseline, while CRP, COMP and ESR were not higher. Conclusions S100A8/A9 aggravate Osteophyte formation in experimental OA with high synovial activation and may be used to predict Osteophyte formation in early human OA. References van Lent PL, Blom AB, Schelbergen RF, Sloetjes A, Lafeber FP, Lems WF, et al. Active involvement of alarmins S100A8 and S100A9 in the regulation of synovial activation and joint destruction during mouse and human osteoarthritis. Arthritis and rheumatism. 2012 May; 64(5):1466-1476 Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.3178
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A5.11 alarmins S100A8/S100A9 stimulate Osteophyte formation in experimental osteoarthritis and predict Osteophyte progression in early human osteoarthritis
Annals of the Rheumatic Diseases, 2014Co-Authors: R.f. Schelbergen, P M Van Der Kraan, W B Van Den Berg, W. De Munter, M.h. Van Den Bosch, F.p.j.g. Lafeber, Annet W. Sloetjes, Thomas Vogl, Johannes Roth, Arjen B. BlomAbstract:Background and Objectives The main pathological feature of osteoarthritis (OA) is degradation of the articular cartilage. However, other important hallmarks include subclinical inflammation of the synovium and ectopic formation of new bone and cartilage at the ligaments or joint margins, termed Osteophytes. Selective depletion of synovial macrophages prevents development of Osteophytes in collagenase induced OA. Alarmins S100A8 and S100A9 are major products of activated macrophages regulating cartilage damage and synovial activation during murine and human osteoarthritis (OA). In the current study we investigated whether S100A8 and S100A9 are involved in Osteophyte formation during experimental OA and if S100A8/A9 predicts Osteophyte progression in early human OA. Materials and Methods OA was elicited in S100A9 -/- and wild-type C57Bl/6 mice in two experimental models that differ in degree of synovial activation. Osteophyte size, S100A8, S100A9 and VDIPEN expression was measured histologically. Chondrogenesis was induced in murine mesenchymal stem cells in the presence of S100A8. Levels of S100A8/A9 were determined in plasma of early symptomatic OA patients of the CHECK cohort study at baseline and development of Osteophytes measured after 2 and 5 years. Results S100A8 and S100A9 protein levels in the synovial lining and serum coincide with Osteophyte development in collagenase-induced OA (CIOA), in which synovial activation is high. Osteophyte size was drastically reduced in S100A9 -/- mice on day 21 and 42 of CIOA, in the medial collateral ligaments (58% and 93% reduction) and at medial femur and tibia (62% and 67% reduction). In contrast, Osteophyte size was not reduced in S100A9 -/- mice during destabilised medial meniscus OA, in which synovial activation is scant. S100A8 increased expression and activation of MMPs during micromass chondrogenesis, thereby possibly increasing cartilage matrix remodelling allowing for larger Osteophytes. Interestingly, early symptomatic OA patients of the CHECK study with Osteophyte progression after two and five years had significantly elevated S100A8/A9 plasma levels at baseline, while CRP, COMP and ESR were not higher. Conclusions S100A8/A9 stimulate Osteophyte formation in experimental OA with high synovial activation and may be used as a marker to predict Osteophyte formation in early human OA.
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resemblance of Osteophytes in experimental osteoarthritis to transforming growth factor β induced Osteophytes limited role of bone morphogenetic protein in early osteoarthritic Osteophyte formation
Arthritis & Rheumatism, 2007Co-Authors: E Blaney N Davidson, E L Vitters, W B Van Den Berg, H Van Beuningen, P M Van Der KraanAbstract:OBJECTIVE: Osteoarthritis (OA) is characterized by cartilage damage, synovial fibrosis, and Osteophyte formation. Both transforming growth factor beta (TGFbeta) and bone morphogenetic protein 2 (BMP-2) can induce the formation of Osteophytes during OA, but their specific role in this process is unclear. The purpose of this study was to investigate the respective contributions of TGFbeta and BMP-2 to OA. METHODS: Mouse knee joints injected with adenovirus (Ad-TGFbeta or Ad-BMP-2) were compared histologically with knee joints from murine models of OA (joints injected with collagenase and joints from STR/Ort mice with spontaneous OA). To further investigate the role of BMP during Osteophyte formation, adenovirus Ad-Gremlin was injected into knee joints that had previously been injected with Ad-TGFbeta or collagenase. RESULTS: BMP-2 induced early Osteophytes, which bulged from the growth plates on the femur and grew on top of the patella, whereas TGFbeta induced early Osteophyte formation on the bone shaft beneath the collateral ligament on the femur as well as on top of the patella. The pattern of Osteophyte formation during experimental OA closely resembled that of TGFbeta-induced Osteophyte formation, but differed from the pattern induced by BMP-2. Ad-Gremlin proved to be able to totally block BMP-2-induced Osteophyte formation. However, blocking BMP activity inhibited neither TGFbeta-induced nor experimental OA-associated Osteophyte formation. CONCLUSION: Our findings demonstrate that the role of BMP during the onset of TGFbeta-induced and experimental OA-induced Osteophyte formation is limited. The latter finding does not rule out a role of BMP during Osteophyte maturation.
P M Van Der Kraan - One of the best experts on this subject based on the ideXlab platform.
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alarmins s100a8 s100a9 aggravate Osteophyte formation in experimental osteoarthritis and predict Osteophyte progression in early human symptomatic osteoarthritis
Annals of the Rheumatic Diseases, 2016Co-Authors: R.f. Schelbergen, P M Van Der Kraan, W B Van Den Berg, W. De Munter, M.h. Van Den Bosch, F.p.j.g. Lafeber, Annet W. Sloetjes, Thomas Vogl, Johannes Roth, Arjen B. BlomAbstract:OBJECTIVE: Alarmins S100A8 and S100A9 are major products of activated macrophages regulating cartilage damage and synovial activation during murine and human osteoarthritis (OA). In the current study, we investigated whether S100A8 and S100A9 are involved in Osteophyte formation during experimental OA and whether S100A8/A9 predicts Osteophyte progression in early human OA. METHODS: OA was elicited in S100A9-/- mice in two experimental models that differ in degree of synovial activation. Osteophyte size, S100A8, S100A9 and VDIPEN neoepitope was measured histologically. Chondrogenesis was induced in murine mesenchymal stem cells in the presence of S100A8. Levels of S100A8/A9 were determined in plasma of early symptomatic OA participants of the Cohort Hip and Cohort Knee (CHECK) cohort study and Osteophytes measured after 2 and 5 years. RESULTS: Osteophyte size was drastically reduced in S100A9-/- mice in ligaments and at medial femur and tibia on days 21 and 42 of collagenase-induced OA, in which synovial activation is high. In contrast, Osteophyte size was not reduced in S100A9-/- mice during destabilised medial meniscus OA, in which synovial activation is scant. S100A8 increased expression and activation of matrix metalloproteinases during micromass chondrogenesis, thereby possibly increasing cartilage matrix remodelling allowing for larger Osteophytes. Interestingly, early symptomatic OA participants of the CHECK study with Osteophyte progression after 2 and 5 years had elevated S100A8/A9 plasma levels at baseline, while C-reactive protein, erythrocyte sedimentation rate and cartilage oligomeric matrix protein were not elevated at baseline. CONCLUSIONS: S100A8/A9 aggravate Osteophyte formation in experimental OA with high synovial activation and may be used to predict Osteophyte progression in early symptomatic human OA.
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Alarmins S100A8/S100A9 aggravate Osteophyte formation in experimental osteoarthritis and predict Osteophyte progression in early human symptomatic osteoarthritis
Annals of the Rheumatic Diseases, 2014Co-Authors: R.f. Schelbergen, P M Van Der Kraan, W B Van Den Berg, W. De Munter, M.h. Van Den Bosch, F.p.j.g. Lafeber, Annet W. Sloetjes, Thomas Vogl, Johannes Roth, Arjen B. BlomAbstract:OBJECTIVE: Alarmins S100A8 and S100A9 are major products of activated macrophages regulating cartilage damage and synovial activation during murine and human osteoarthritis (OA). In the current study, we investigated whether S100A8 and S100A9 are involved in Osteophyte formation during experimental OA and whether S100A8/A9 predicts Osteophyte progression in early human OA. METHODS: OA was elicited in S100A9-/- mice in two experimental models that differ in degree of synovial activation. Osteophyte size, S100A8, S100A9 and VDIPEN neoepitope was measured histologically. Chondrogenesis was induced in murine mesenchymal stem cells in the presence of S100A8. Levels of S100A8/A9 were determined in plasma of early symptomatic OA participants of the Cohort Hip and Cohort Knee (CHECK) cohort study and Osteophytes measured after 2 and 5 years. RESULTS: Osteophyte size was drastically reduced in S100A9-/- mice in ligaments and at medial femur and tibia on days 21 and 42 of collagenase-induced OA, in which synovial activation is high. In contrast, Osteophyte size was not reduced in S100A9-/- mice during destabilised medial meniscus OA, in which synovial activation is scant. S100A8 increased expression and activation of matrix metalloproteinases during micromass chondrogenesis, thereby possibly increasing cartilage matrix remodelling allowing for larger Osteophytes. Interestingly, early symptomatic OA participants of the CHECK study with Osteophyte progression after 2 and 5 years had elevated S100A8/A9 plasma levels at baseline, while C-reactive protein, erythrocyte sedimentation rate and cartilage oligomeric matrix protein were not elevated at baseline. CONCLUSIONS: S100A8/A9 aggravate Osteophyte formation in experimental OA with high synovial activation and may be used to predict Osteophyte progression in early symptomatic human OA.
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OP0146 Alarmins S100a8/S100a9 Aggravate Osteophyte Formation in Experimental Osteoarthritis and PREDICT Osteophyte Progression in Early Human Osteoarthritis in the Dutch CHECK Cohort
Annals of the Rheumatic Diseases, 2014Co-Authors: R.f. Schelbergen, P M Van Der Kraan, W B Van Den Berg, W. De Munter, M.h. Van Den Bosch, F.p.j.g. Lafeber, Annet W. Sloetjes, Thomas Vogl, Johannes Roth, Arjen B. BlomAbstract:Background The main pathological feature of osteoarthritis (OA) is degradation of the articular cartilage. Other important hallmarks include subclinical inflammation of the synovium and ectopic formation of new bone and cartilage at the ligaments or joint margins, termed Osteophytes. Alarmins S100A8 and S100A9 are major products of activated macrophages regulating cartilage damage and synovial activation during murine and human osteoarthritis (1) (OA). Objectives In the current study we investigated whether S100A8 and S100A9 are involved in Osteophyte formation during experimental OA and if S100A8/A9 predicts Osteophyte progression in early human OA. Methods OA was elicited in S100A9 -/- and wild-type C57Bl/6 mice in two experimental models that differ in degree of synovial activation. Osteophyte size, S100A8, S100A9 and VDIPEN expression was measured on histology. Chondrogenesis was induced in murine mesenchymal stem cells (MSCs) in the presence of S100A8. Levels of S100A8/A9 were determined in plasma of early symptomatic OA patients of the CHECK cohort study and Osteophyte size measured at baseline and after 2 and 5 years. Results S100A8 and S100A9 protein levels in the synovial lining and serum coincide with Osteophyte development in collagenase-induced OA (CIOA), in which synovial activation is high. Osteophyte size was drastically reduced in S100A9 -/- mice on day 21 and 42 of CIOA, in the medial collateral ligaments (58% and 93% reduction) and at medial femur and tibia (62% and 67% reduction). In contrast, Osteophyte size was not reduced in S100A9 -/- mice during destabilized medial meniscus OA, in which synovial activation is scant. One explanation for the reduced Osteophyte size in S100A9-/- mice may be a direct effect of S100-proteins on chondrogenesis. During in vitro chondrogenesis using murine MSCs, S100A8 caused a marked increase in MMP-3 mRNA and VDIPEN expression (as measure for MMP activity) as well as a strongly altered morphology, indicating increased remodeling allowing for larger Osteophytes. Interestingly, early symptomatic OA patients of the CHECK study with Osteophyte progression after two and five years had significantly elevated S100A8/A9 plasma levels at baseline, while CRP, COMP and ESR were not higher. Conclusions S100A8/A9 aggravate Osteophyte formation in experimental OA with high synovial activation and may be used to predict Osteophyte formation in early human OA. References van Lent PL, Blom AB, Schelbergen RF, Sloetjes A, Lafeber FP, Lems WF, et al. Active involvement of alarmins S100A8 and S100A9 in the regulation of synovial activation and joint destruction during mouse and human osteoarthritis. Arthritis and rheumatism. 2012 May; 64(5):1466-1476 Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.3178
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A5.11 alarmins S100A8/S100A9 stimulate Osteophyte formation in experimental osteoarthritis and predict Osteophyte progression in early human osteoarthritis
Annals of the Rheumatic Diseases, 2014Co-Authors: R.f. Schelbergen, P M Van Der Kraan, W B Van Den Berg, W. De Munter, M.h. Van Den Bosch, F.p.j.g. Lafeber, Annet W. Sloetjes, Thomas Vogl, Johannes Roth, Arjen B. BlomAbstract:Background and Objectives The main pathological feature of osteoarthritis (OA) is degradation of the articular cartilage. However, other important hallmarks include subclinical inflammation of the synovium and ectopic formation of new bone and cartilage at the ligaments or joint margins, termed Osteophytes. Selective depletion of synovial macrophages prevents development of Osteophytes in collagenase induced OA. Alarmins S100A8 and S100A9 are major products of activated macrophages regulating cartilage damage and synovial activation during murine and human osteoarthritis (OA). In the current study we investigated whether S100A8 and S100A9 are involved in Osteophyte formation during experimental OA and if S100A8/A9 predicts Osteophyte progression in early human OA. Materials and Methods OA was elicited in S100A9 -/- and wild-type C57Bl/6 mice in two experimental models that differ in degree of synovial activation. Osteophyte size, S100A8, S100A9 and VDIPEN expression was measured histologically. Chondrogenesis was induced in murine mesenchymal stem cells in the presence of S100A8. Levels of S100A8/A9 were determined in plasma of early symptomatic OA patients of the CHECK cohort study at baseline and development of Osteophytes measured after 2 and 5 years. Results S100A8 and S100A9 protein levels in the synovial lining and serum coincide with Osteophyte development in collagenase-induced OA (CIOA), in which synovial activation is high. Osteophyte size was drastically reduced in S100A9 -/- mice on day 21 and 42 of CIOA, in the medial collateral ligaments (58% and 93% reduction) and at medial femur and tibia (62% and 67% reduction). In contrast, Osteophyte size was not reduced in S100A9 -/- mice during destabilised medial meniscus OA, in which synovial activation is scant. S100A8 increased expression and activation of MMPs during micromass chondrogenesis, thereby possibly increasing cartilage matrix remodelling allowing for larger Osteophytes. Interestingly, early symptomatic OA patients of the CHECK study with Osteophyte progression after two and five years had significantly elevated S100A8/A9 plasma levels at baseline, while CRP, COMP and ESR were not higher. Conclusions S100A8/A9 stimulate Osteophyte formation in experimental OA with high synovial activation and may be used as a marker to predict Osteophyte formation in early human OA.
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resemblance of Osteophytes in experimental osteoarthritis to transforming growth factor β induced Osteophytes limited role of bone morphogenetic protein in early osteoarthritic Osteophyte formation
Arthritis & Rheumatism, 2007Co-Authors: E Blaney N Davidson, E L Vitters, W B Van Den Berg, H Van Beuningen, P M Van Der KraanAbstract:OBJECTIVE: Osteoarthritis (OA) is characterized by cartilage damage, synovial fibrosis, and Osteophyte formation. Both transforming growth factor beta (TGFbeta) and bone morphogenetic protein 2 (BMP-2) can induce the formation of Osteophytes during OA, but their specific role in this process is unclear. The purpose of this study was to investigate the respective contributions of TGFbeta and BMP-2 to OA. METHODS: Mouse knee joints injected with adenovirus (Ad-TGFbeta or Ad-BMP-2) were compared histologically with knee joints from murine models of OA (joints injected with collagenase and joints from STR/Ort mice with spontaneous OA). To further investigate the role of BMP during Osteophyte formation, adenovirus Ad-Gremlin was injected into knee joints that had previously been injected with Ad-TGFbeta or collagenase. RESULTS: BMP-2 induced early Osteophytes, which bulged from the growth plates on the femur and grew on top of the patella, whereas TGFbeta induced early Osteophyte formation on the bone shaft beneath the collateral ligament on the femur as well as on top of the patella. The pattern of Osteophyte formation during experimental OA closely resembled that of TGFbeta-induced Osteophyte formation, but differed from the pattern induced by BMP-2. Ad-Gremlin proved to be able to totally block BMP-2-induced Osteophyte formation. However, blocking BMP activity inhibited neither TGFbeta-induced nor experimental OA-associated Osteophyte formation. CONCLUSION: Our findings demonstrate that the role of BMP during the onset of TGFbeta-induced and experimental OA-induced Osteophyte formation is limited. The latter finding does not rule out a role of BMP during Osteophyte maturation.
Arjen B. Blom - One of the best experts on this subject based on the ideXlab platform.
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alarmins s100a8 s100a9 aggravate Osteophyte formation in experimental osteoarthritis and predict Osteophyte progression in early human symptomatic osteoarthritis
Annals of the Rheumatic Diseases, 2016Co-Authors: R.f. Schelbergen, P M Van Der Kraan, W B Van Den Berg, W. De Munter, M.h. Van Den Bosch, F.p.j.g. Lafeber, Annet W. Sloetjes, Thomas Vogl, Johannes Roth, Arjen B. BlomAbstract:OBJECTIVE: Alarmins S100A8 and S100A9 are major products of activated macrophages regulating cartilage damage and synovial activation during murine and human osteoarthritis (OA). In the current study, we investigated whether S100A8 and S100A9 are involved in Osteophyte formation during experimental OA and whether S100A8/A9 predicts Osteophyte progression in early human OA. METHODS: OA was elicited in S100A9-/- mice in two experimental models that differ in degree of synovial activation. Osteophyte size, S100A8, S100A9 and VDIPEN neoepitope was measured histologically. Chondrogenesis was induced in murine mesenchymal stem cells in the presence of S100A8. Levels of S100A8/A9 were determined in plasma of early symptomatic OA participants of the Cohort Hip and Cohort Knee (CHECK) cohort study and Osteophytes measured after 2 and 5 years. RESULTS: Osteophyte size was drastically reduced in S100A9-/- mice in ligaments and at medial femur and tibia on days 21 and 42 of collagenase-induced OA, in which synovial activation is high. In contrast, Osteophyte size was not reduced in S100A9-/- mice during destabilised medial meniscus OA, in which synovial activation is scant. S100A8 increased expression and activation of matrix metalloproteinases during micromass chondrogenesis, thereby possibly increasing cartilage matrix remodelling allowing for larger Osteophytes. Interestingly, early symptomatic OA participants of the CHECK study with Osteophyte progression after 2 and 5 years had elevated S100A8/A9 plasma levels at baseline, while C-reactive protein, erythrocyte sedimentation rate and cartilage oligomeric matrix protein were not elevated at baseline. CONCLUSIONS: S100A8/A9 aggravate Osteophyte formation in experimental OA with high synovial activation and may be used to predict Osteophyte progression in early symptomatic human OA.
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Alarmins S100A8/S100A9 aggravate Osteophyte formation in experimental osteoarthritis and predict Osteophyte progression in early human symptomatic osteoarthritis
Annals of the Rheumatic Diseases, 2014Co-Authors: R.f. Schelbergen, P M Van Der Kraan, W B Van Den Berg, W. De Munter, M.h. Van Den Bosch, F.p.j.g. Lafeber, Annet W. Sloetjes, Thomas Vogl, Johannes Roth, Arjen B. BlomAbstract:OBJECTIVE: Alarmins S100A8 and S100A9 are major products of activated macrophages regulating cartilage damage and synovial activation during murine and human osteoarthritis (OA). In the current study, we investigated whether S100A8 and S100A9 are involved in Osteophyte formation during experimental OA and whether S100A8/A9 predicts Osteophyte progression in early human OA. METHODS: OA was elicited in S100A9-/- mice in two experimental models that differ in degree of synovial activation. Osteophyte size, S100A8, S100A9 and VDIPEN neoepitope was measured histologically. Chondrogenesis was induced in murine mesenchymal stem cells in the presence of S100A8. Levels of S100A8/A9 were determined in plasma of early symptomatic OA participants of the Cohort Hip and Cohort Knee (CHECK) cohort study and Osteophytes measured after 2 and 5 years. RESULTS: Osteophyte size was drastically reduced in S100A9-/- mice in ligaments and at medial femur and tibia on days 21 and 42 of collagenase-induced OA, in which synovial activation is high. In contrast, Osteophyte size was not reduced in S100A9-/- mice during destabilised medial meniscus OA, in which synovial activation is scant. S100A8 increased expression and activation of matrix metalloproteinases during micromass chondrogenesis, thereby possibly increasing cartilage matrix remodelling allowing for larger Osteophytes. Interestingly, early symptomatic OA participants of the CHECK study with Osteophyte progression after 2 and 5 years had elevated S100A8/A9 plasma levels at baseline, while C-reactive protein, erythrocyte sedimentation rate and cartilage oligomeric matrix protein were not elevated at baseline. CONCLUSIONS: S100A8/A9 aggravate Osteophyte formation in experimental OA with high synovial activation and may be used to predict Osteophyte progression in early symptomatic human OA.
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OP0146 Alarmins S100a8/S100a9 Aggravate Osteophyte Formation in Experimental Osteoarthritis and PREDICT Osteophyte Progression in Early Human Osteoarthritis in the Dutch CHECK Cohort
Annals of the Rheumatic Diseases, 2014Co-Authors: R.f. Schelbergen, P M Van Der Kraan, W B Van Den Berg, W. De Munter, M.h. Van Den Bosch, F.p.j.g. Lafeber, Annet W. Sloetjes, Thomas Vogl, Johannes Roth, Arjen B. BlomAbstract:Background The main pathological feature of osteoarthritis (OA) is degradation of the articular cartilage. Other important hallmarks include subclinical inflammation of the synovium and ectopic formation of new bone and cartilage at the ligaments or joint margins, termed Osteophytes. Alarmins S100A8 and S100A9 are major products of activated macrophages regulating cartilage damage and synovial activation during murine and human osteoarthritis (1) (OA). Objectives In the current study we investigated whether S100A8 and S100A9 are involved in Osteophyte formation during experimental OA and if S100A8/A9 predicts Osteophyte progression in early human OA. Methods OA was elicited in S100A9 -/- and wild-type C57Bl/6 mice in two experimental models that differ in degree of synovial activation. Osteophyte size, S100A8, S100A9 and VDIPEN expression was measured on histology. Chondrogenesis was induced in murine mesenchymal stem cells (MSCs) in the presence of S100A8. Levels of S100A8/A9 were determined in plasma of early symptomatic OA patients of the CHECK cohort study and Osteophyte size measured at baseline and after 2 and 5 years. Results S100A8 and S100A9 protein levels in the synovial lining and serum coincide with Osteophyte development in collagenase-induced OA (CIOA), in which synovial activation is high. Osteophyte size was drastically reduced in S100A9 -/- mice on day 21 and 42 of CIOA, in the medial collateral ligaments (58% and 93% reduction) and at medial femur and tibia (62% and 67% reduction). In contrast, Osteophyte size was not reduced in S100A9 -/- mice during destabilized medial meniscus OA, in which synovial activation is scant. One explanation for the reduced Osteophyte size in S100A9-/- mice may be a direct effect of S100-proteins on chondrogenesis. During in vitro chondrogenesis using murine MSCs, S100A8 caused a marked increase in MMP-3 mRNA and VDIPEN expression (as measure for MMP activity) as well as a strongly altered morphology, indicating increased remodeling allowing for larger Osteophytes. Interestingly, early symptomatic OA patients of the CHECK study with Osteophyte progression after two and five years had significantly elevated S100A8/A9 plasma levels at baseline, while CRP, COMP and ESR were not higher. Conclusions S100A8/A9 aggravate Osteophyte formation in experimental OA with high synovial activation and may be used to predict Osteophyte formation in early human OA. References van Lent PL, Blom AB, Schelbergen RF, Sloetjes A, Lafeber FP, Lems WF, et al. Active involvement of alarmins S100A8 and S100A9 in the regulation of synovial activation and joint destruction during mouse and human osteoarthritis. Arthritis and rheumatism. 2012 May; 64(5):1466-1476 Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.3178
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A5.11 alarmins S100A8/S100A9 stimulate Osteophyte formation in experimental osteoarthritis and predict Osteophyte progression in early human osteoarthritis
Annals of the Rheumatic Diseases, 2014Co-Authors: R.f. Schelbergen, P M Van Der Kraan, W B Van Den Berg, W. De Munter, M.h. Van Den Bosch, F.p.j.g. Lafeber, Annet W. Sloetjes, Thomas Vogl, Johannes Roth, Arjen B. BlomAbstract:Background and Objectives The main pathological feature of osteoarthritis (OA) is degradation of the articular cartilage. However, other important hallmarks include subclinical inflammation of the synovium and ectopic formation of new bone and cartilage at the ligaments or joint margins, termed Osteophytes. Selective depletion of synovial macrophages prevents development of Osteophytes in collagenase induced OA. Alarmins S100A8 and S100A9 are major products of activated macrophages regulating cartilage damage and synovial activation during murine and human osteoarthritis (OA). In the current study we investigated whether S100A8 and S100A9 are involved in Osteophyte formation during experimental OA and if S100A8/A9 predicts Osteophyte progression in early human OA. Materials and Methods OA was elicited in S100A9 -/- and wild-type C57Bl/6 mice in two experimental models that differ in degree of synovial activation. Osteophyte size, S100A8, S100A9 and VDIPEN expression was measured histologically. Chondrogenesis was induced in murine mesenchymal stem cells in the presence of S100A8. Levels of S100A8/A9 were determined in plasma of early symptomatic OA patients of the CHECK cohort study at baseline and development of Osteophytes measured after 2 and 5 years. Results S100A8 and S100A9 protein levels in the synovial lining and serum coincide with Osteophyte development in collagenase-induced OA (CIOA), in which synovial activation is high. Osteophyte size was drastically reduced in S100A9 -/- mice on day 21 and 42 of CIOA, in the medial collateral ligaments (58% and 93% reduction) and at medial femur and tibia (62% and 67% reduction). In contrast, Osteophyte size was not reduced in S100A9 -/- mice during destabilised medial meniscus OA, in which synovial activation is scant. S100A8 increased expression and activation of MMPs during micromass chondrogenesis, thereby possibly increasing cartilage matrix remodelling allowing for larger Osteophytes. Interestingly, early symptomatic OA patients of the CHECK study with Osteophyte progression after two and five years had significantly elevated S100A8/A9 plasma levels at baseline, while CRP, COMP and ESR were not higher. Conclusions S100A8/A9 stimulate Osteophyte formation in experimental OA with high synovial activation and may be used as a marker to predict Osteophyte formation in early human OA.
H Van Beuningen - One of the best experts on this subject based on the ideXlab platform.
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resemblance of Osteophytes in experimental osteoarthritis to transforming growth factor β induced Osteophytes limited role of bone morphogenetic protein in early osteoarthritic Osteophyte formation
Arthritis & Rheumatism, 2007Co-Authors: E Blaney N Davidson, E L Vitters, W B Van Den Berg, H Van Beuningen, P M Van Der KraanAbstract:OBJECTIVE: Osteoarthritis (OA) is characterized by cartilage damage, synovial fibrosis, and Osteophyte formation. Both transforming growth factor beta (TGFbeta) and bone morphogenetic protein 2 (BMP-2) can induce the formation of Osteophytes during OA, but their specific role in this process is unclear. The purpose of this study was to investigate the respective contributions of TGFbeta and BMP-2 to OA. METHODS: Mouse knee joints injected with adenovirus (Ad-TGFbeta or Ad-BMP-2) were compared histologically with knee joints from murine models of OA (joints injected with collagenase and joints from STR/Ort mice with spontaneous OA). To further investigate the role of BMP during Osteophyte formation, adenovirus Ad-Gremlin was injected into knee joints that had previously been injected with Ad-TGFbeta or collagenase. RESULTS: BMP-2 induced early Osteophytes, which bulged from the growth plates on the femur and grew on top of the patella, whereas TGFbeta induced early Osteophyte formation on the bone shaft beneath the collateral ligament on the femur as well as on top of the patella. The pattern of Osteophyte formation during experimental OA closely resembled that of TGFbeta-induced Osteophyte formation, but differed from the pattern induced by BMP-2. Ad-Gremlin proved to be able to totally block BMP-2-induced Osteophyte formation. However, blocking BMP activity inhibited neither TGFbeta-induced nor experimental OA-associated Osteophyte formation. CONCLUSION: Our findings demonstrate that the role of BMP during the onset of TGFbeta-induced and experimental OA-induced Osteophyte formation is limited. The latter finding does not rule out a role of BMP during Osteophyte maturation.
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Resemblance of Osteophytes in experimental osteoarthritis to transforming growth factor β–induced Osteophytes: Limited role of bone morphogenetic protein in early osteoarthritic Osteophyte formation
Arthritis & Rheumatism, 2007Co-Authors: E.n. Blaney Davidson, H Van Beuningen, W B Van Den Berg, Elly L. Vitters, P M Van Der KraanAbstract:OBJECTIVE: Osteoarthritis (OA) is characterized by cartilage damage, synovial fibrosis, and Osteophyte formation. Both transforming growth factor beta (TGFbeta) and bone morphogenetic protein 2 (BMP-2) can induce the formation of Osteophytes during OA, but their specific role in this process is unclear. The purpose of this study was to investigate the respective contributions of TGFbeta and BMP-2 to OA. METHODS: Mouse knee joints injected with adenovirus (Ad-TGFbeta or Ad-BMP-2) were compared histologically with knee joints from murine models of OA (joints injected with collagenase and joints from STR/Ort mice with spontaneous OA). To further investigate the role of BMP during Osteophyte formation, adenovirus Ad-Gremlin was injected into knee joints that had previously been injected with Ad-TGFbeta or collagenase. RESULTS: BMP-2 induced early Osteophytes, which bulged from the growth plates on the femur and grew on top of the patella, whereas TGFbeta induced early Osteophyte formation on the bone shaft beneath the collateral ligament on the femur as well as on top of the patella. The pattern of Osteophyte formation during experimental OA closely resembled that of TGFbeta-induced Osteophyte formation, but differed from the pattern induced by BMP-2. Ad-Gremlin proved to be able to totally block BMP-2-induced Osteophyte formation. However, blocking BMP activity inhibited neither TGFbeta-induced nor experimental OA-associated Osteophyte formation. CONCLUSION: Our findings demonstrate that the role of BMP during the onset of TGFbeta-induced and experimental OA-induced Osteophyte formation is limited. The latter finding does not rule out a role of BMP during Osteophyte maturation.
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transforming growth factor beta 1 stimulates articular chondrocyte proteoglycan synthesis and induces Osteophyte formation in the murine knee joint
Laboratory Investigation, 1994Co-Authors: H Van Beuningen, P M Van Der Kraan, O J Arntz, W B Van Den BergAbstract:BACKGROUND: High concentrations of active transforming growth factor-beta (TGF-beta) have been found in synovial fluids from arthritic joints. TGF-beta stimulates articular cartilage proteoglycan synthesis and suppresses proteoglycan degradation in vitro. In an earlier study, we found no effect on cartilage proteoglycan metabolism shortly after a single intra-articular injection of TGF-beta 1. In the present study, we used multiple intra-articular injections and a longer time-scale. EXPERIMENTAL DESIGN: TGF-beta 1 was injected into the murine knee joint to gain insight in the consequences of its overproduction in joint diseases. This was evaluated using histologic sections of the whole knee joint and measurements of articular cartilage proteoglycan synthesis and content. RESULTS: At 6 hours after a single TGF-beta 1 injection, recruitment of polymorphonuclear leukocytes (PMNs) was observed. After 24 hours, the amount of inflammatory cells had already decreased. Multiple TGF-beta 1 injections induced synovial hyperplasia and synovitis predominantly consisting of cells of the macrophage/monocyte lineage. Both single and multiple TGF-beta 1 injections induced strong and long-lasting stimulation of articular cartilage proteoglycan synthesis. This in vivo stimulation of proteoglycan synthesis was similar in cartilage of young (3 months) and old mice (18 months). Multiple TGF-beta 1 injections resulted in an increased GAG content in patellar cartilage. After triple TGF-beta 1 injections, impressive Osteophyte formation was noted at specific sites. The size and the localization of Osteophytes was identical in young and old mice. Interestingly, the localization of TGF-beta 1-induced Osteophytes was very similar to that of Osteophytes observed in experimental arthritis and osteoarthritis models, suggesting a role for endogenous TGF-beta in Osteophyte formation during joint pathology. CONCLUSIONS: Our data indicate that TGF-beta 1 injection into a normal joint induces inflammation, synovial hyperplasia, Osteophyte formation, and prolonged elevation of proteoglycan synthesis and content in articular cartilage.
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Cartilage destruction and Osteophytes in instability-induced murine osteoarthritis: Role of TGFβ in Osteophyte formation?
Inflammation Research, 1993Co-Authors: W B Van Den Berg, P M Van Der Kraan, G J Van Osch, H Van BeuningenAbstract:Osteoarthritis is characterized by focal cartilage destruction and marked formation of Osteophytes. We have investigated the possible relationship between site specific occurrence of cartilage damage and Osteophytes in the collagenase induced murine osteoarthritis model. The degree of instability of the joint correlated with the amount of cartilage loss. Moreover, cartilage damage in the medial tibial plateau correlated only strongly with the Osteophyte at the medial plateau, whereas a similar, site directed trend was noted for lateral damage and lateral Osteophytes. A separate study with intraarticular injection of TGFβ1 in normal murine knee joints revealed that this factor can induce Osteophytes at characteristic sites, suggesting a role of endogenous TGFβ in this phenomenon.
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Cartilage destruction and Osteophytes in instability-induced murine osteoarthritis: role of TGF beta in Osteophyte formation?
Agents and actions, 1993Co-Authors: W B Van Den Berg, P M Van Der Kraan, G J Van Osch, H Van BeuningenAbstract:Osteoarthritis is characterized by focal cartilage destruction and marked formation of Osteophytes. We have investigated the possible relationship between site specific occurrence of cartilage damage and Osteophytes in the collagenase induced murine osteoarthritis model. The degree of instability of the joint correlated with the amount of cartilage loss. Moreover, cartilage damage in the medial tibial plateau correlated only strongly with the Osteophyte at the medial plateau, whereas a similar, site directed trend was noted for lateral damage and lateral Osteophytes. A separate study with intraarticular injection of TGF beta 1 in normal murine knee joints revealed that this factor can induce Osteophytes at characteristic sites, suggesting a role of endogenous TGF beta in this phenomenon.
Johannes Roth - One of the best experts on this subject based on the ideXlab platform.
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alarmins s100a8 s100a9 aggravate Osteophyte formation in experimental osteoarthritis and predict Osteophyte progression in early human symptomatic osteoarthritis
Annals of the Rheumatic Diseases, 2016Co-Authors: R.f. Schelbergen, P M Van Der Kraan, W B Van Den Berg, W. De Munter, M.h. Van Den Bosch, F.p.j.g. Lafeber, Annet W. Sloetjes, Thomas Vogl, Johannes Roth, Arjen B. BlomAbstract:OBJECTIVE: Alarmins S100A8 and S100A9 are major products of activated macrophages regulating cartilage damage and synovial activation during murine and human osteoarthritis (OA). In the current study, we investigated whether S100A8 and S100A9 are involved in Osteophyte formation during experimental OA and whether S100A8/A9 predicts Osteophyte progression in early human OA. METHODS: OA was elicited in S100A9-/- mice in two experimental models that differ in degree of synovial activation. Osteophyte size, S100A8, S100A9 and VDIPEN neoepitope was measured histologically. Chondrogenesis was induced in murine mesenchymal stem cells in the presence of S100A8. Levels of S100A8/A9 were determined in plasma of early symptomatic OA participants of the Cohort Hip and Cohort Knee (CHECK) cohort study and Osteophytes measured after 2 and 5 years. RESULTS: Osteophyte size was drastically reduced in S100A9-/- mice in ligaments and at medial femur and tibia on days 21 and 42 of collagenase-induced OA, in which synovial activation is high. In contrast, Osteophyte size was not reduced in S100A9-/- mice during destabilised medial meniscus OA, in which synovial activation is scant. S100A8 increased expression and activation of matrix metalloproteinases during micromass chondrogenesis, thereby possibly increasing cartilage matrix remodelling allowing for larger Osteophytes. Interestingly, early symptomatic OA participants of the CHECK study with Osteophyte progression after 2 and 5 years had elevated S100A8/A9 plasma levels at baseline, while C-reactive protein, erythrocyte sedimentation rate and cartilage oligomeric matrix protein were not elevated at baseline. CONCLUSIONS: S100A8/A9 aggravate Osteophyte formation in experimental OA with high synovial activation and may be used to predict Osteophyte progression in early symptomatic human OA.
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Alarmins S100A8/S100A9 aggravate Osteophyte formation in experimental osteoarthritis and predict Osteophyte progression in early human symptomatic osteoarthritis
Annals of the Rheumatic Diseases, 2014Co-Authors: R.f. Schelbergen, P M Van Der Kraan, W B Van Den Berg, W. De Munter, M.h. Van Den Bosch, F.p.j.g. Lafeber, Annet W. Sloetjes, Thomas Vogl, Johannes Roth, Arjen B. BlomAbstract:OBJECTIVE: Alarmins S100A8 and S100A9 are major products of activated macrophages regulating cartilage damage and synovial activation during murine and human osteoarthritis (OA). In the current study, we investigated whether S100A8 and S100A9 are involved in Osteophyte formation during experimental OA and whether S100A8/A9 predicts Osteophyte progression in early human OA. METHODS: OA was elicited in S100A9-/- mice in two experimental models that differ in degree of synovial activation. Osteophyte size, S100A8, S100A9 and VDIPEN neoepitope was measured histologically. Chondrogenesis was induced in murine mesenchymal stem cells in the presence of S100A8. Levels of S100A8/A9 were determined in plasma of early symptomatic OA participants of the Cohort Hip and Cohort Knee (CHECK) cohort study and Osteophytes measured after 2 and 5 years. RESULTS: Osteophyte size was drastically reduced in S100A9-/- mice in ligaments and at medial femur and tibia on days 21 and 42 of collagenase-induced OA, in which synovial activation is high. In contrast, Osteophyte size was not reduced in S100A9-/- mice during destabilised medial meniscus OA, in which synovial activation is scant. S100A8 increased expression and activation of matrix metalloproteinases during micromass chondrogenesis, thereby possibly increasing cartilage matrix remodelling allowing for larger Osteophytes. Interestingly, early symptomatic OA participants of the CHECK study with Osteophyte progression after 2 and 5 years had elevated S100A8/A9 plasma levels at baseline, while C-reactive protein, erythrocyte sedimentation rate and cartilage oligomeric matrix protein were not elevated at baseline. CONCLUSIONS: S100A8/A9 aggravate Osteophyte formation in experimental OA with high synovial activation and may be used to predict Osteophyte progression in early symptomatic human OA.
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OP0146 Alarmins S100a8/S100a9 Aggravate Osteophyte Formation in Experimental Osteoarthritis and PREDICT Osteophyte Progression in Early Human Osteoarthritis in the Dutch CHECK Cohort
Annals of the Rheumatic Diseases, 2014Co-Authors: R.f. Schelbergen, P M Van Der Kraan, W B Van Den Berg, W. De Munter, M.h. Van Den Bosch, F.p.j.g. Lafeber, Annet W. Sloetjes, Thomas Vogl, Johannes Roth, Arjen B. BlomAbstract:Background The main pathological feature of osteoarthritis (OA) is degradation of the articular cartilage. Other important hallmarks include subclinical inflammation of the synovium and ectopic formation of new bone and cartilage at the ligaments or joint margins, termed Osteophytes. Alarmins S100A8 and S100A9 are major products of activated macrophages regulating cartilage damage and synovial activation during murine and human osteoarthritis (1) (OA). Objectives In the current study we investigated whether S100A8 and S100A9 are involved in Osteophyte formation during experimental OA and if S100A8/A9 predicts Osteophyte progression in early human OA. Methods OA was elicited in S100A9 -/- and wild-type C57Bl/6 mice in two experimental models that differ in degree of synovial activation. Osteophyte size, S100A8, S100A9 and VDIPEN expression was measured on histology. Chondrogenesis was induced in murine mesenchymal stem cells (MSCs) in the presence of S100A8. Levels of S100A8/A9 were determined in plasma of early symptomatic OA patients of the CHECK cohort study and Osteophyte size measured at baseline and after 2 and 5 years. Results S100A8 and S100A9 protein levels in the synovial lining and serum coincide with Osteophyte development in collagenase-induced OA (CIOA), in which synovial activation is high. Osteophyte size was drastically reduced in S100A9 -/- mice on day 21 and 42 of CIOA, in the medial collateral ligaments (58% and 93% reduction) and at medial femur and tibia (62% and 67% reduction). In contrast, Osteophyte size was not reduced in S100A9 -/- mice during destabilized medial meniscus OA, in which synovial activation is scant. One explanation for the reduced Osteophyte size in S100A9-/- mice may be a direct effect of S100-proteins on chondrogenesis. During in vitro chondrogenesis using murine MSCs, S100A8 caused a marked increase in MMP-3 mRNA and VDIPEN expression (as measure for MMP activity) as well as a strongly altered morphology, indicating increased remodeling allowing for larger Osteophytes. Interestingly, early symptomatic OA patients of the CHECK study with Osteophyte progression after two and five years had significantly elevated S100A8/A9 plasma levels at baseline, while CRP, COMP and ESR were not higher. Conclusions S100A8/A9 aggravate Osteophyte formation in experimental OA with high synovial activation and may be used to predict Osteophyte formation in early human OA. References van Lent PL, Blom AB, Schelbergen RF, Sloetjes A, Lafeber FP, Lems WF, et al. Active involvement of alarmins S100A8 and S100A9 in the regulation of synovial activation and joint destruction during mouse and human osteoarthritis. Arthritis and rheumatism. 2012 May; 64(5):1466-1476 Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.3178
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A5.11 alarmins S100A8/S100A9 stimulate Osteophyte formation in experimental osteoarthritis and predict Osteophyte progression in early human osteoarthritis
Annals of the Rheumatic Diseases, 2014Co-Authors: R.f. Schelbergen, P M Van Der Kraan, W B Van Den Berg, W. De Munter, M.h. Van Den Bosch, F.p.j.g. Lafeber, Annet W. Sloetjes, Thomas Vogl, Johannes Roth, Arjen B. BlomAbstract:Background and Objectives The main pathological feature of osteoarthritis (OA) is degradation of the articular cartilage. However, other important hallmarks include subclinical inflammation of the synovium and ectopic formation of new bone and cartilage at the ligaments or joint margins, termed Osteophytes. Selective depletion of synovial macrophages prevents development of Osteophytes in collagenase induced OA. Alarmins S100A8 and S100A9 are major products of activated macrophages regulating cartilage damage and synovial activation during murine and human osteoarthritis (OA). In the current study we investigated whether S100A8 and S100A9 are involved in Osteophyte formation during experimental OA and if S100A8/A9 predicts Osteophyte progression in early human OA. Materials and Methods OA was elicited in S100A9 -/- and wild-type C57Bl/6 mice in two experimental models that differ in degree of synovial activation. Osteophyte size, S100A8, S100A9 and VDIPEN expression was measured histologically. Chondrogenesis was induced in murine mesenchymal stem cells in the presence of S100A8. Levels of S100A8/A9 were determined in plasma of early symptomatic OA patients of the CHECK cohort study at baseline and development of Osteophytes measured after 2 and 5 years. Results S100A8 and S100A9 protein levels in the synovial lining and serum coincide with Osteophyte development in collagenase-induced OA (CIOA), in which synovial activation is high. Osteophyte size was drastically reduced in S100A9 -/- mice on day 21 and 42 of CIOA, in the medial collateral ligaments (58% and 93% reduction) and at medial femur and tibia (62% and 67% reduction). In contrast, Osteophyte size was not reduced in S100A9 -/- mice during destabilised medial meniscus OA, in which synovial activation is scant. S100A8 increased expression and activation of MMPs during micromass chondrogenesis, thereby possibly increasing cartilage matrix remodelling allowing for larger Osteophytes. Interestingly, early symptomatic OA patients of the CHECK study with Osteophyte progression after two and five years had significantly elevated S100A8/A9 plasma levels at baseline, while CRP, COMP and ESR were not higher. Conclusions S100A8/A9 stimulate Osteophyte formation in experimental OA with high synovial activation and may be used as a marker to predict Osteophyte formation in early human OA.
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synovial lining macrophages mediate Osteophyte formation during experimental osteoarthritis
Osteoarthritis and Cartilage, 2004Co-Authors: A B Blom, Peter M. Van Der Kraan, Johannes Roth, Peter L E M Van Lent, A E M Holthuysen, Nico Van Rooijen, Wim B. Van Den BergAbstract:OBJECTIVE: In human osteoarthritis (OA), various forms of pathology are observed. Besides cartilage damage and fibrosis, neogenesis of bone, Osteophyte formation, also occurs. Osteophytes are thought to limit joint movement and cause pain. The objective of this study was to investigate whether synovial macrophages are involved in Osteophyte formation in experimental OA, and if they are, to study which mechanism may be involved. DESIGN: Experimental OA was induced by two intra-articular injections of collagenase on alternate days into murine knee joints. The role of synovial lining macrophages in this model was studied by selective removal of these cells prior to OA induction using clodronate liposomes. After 1 and 2 weeks, knee joints were dissected and examined (immuno)histologically. RESULTS: At days 7 and 14 after induction of OA, Osteophyte formation and fibrosis were observed. Depletion of synovial macrophages resulted in spectacular reduction of Osteophyte formation, 84% and 66%, respectively, at days 7 and 14. Fibrosis and synovial activation, measured by MRP8/14 expression, were also ameliorated (40-60%). In addition, production of growth factors (TGFbeta, BMP-2 and BMP-4) in the lining was largely prevented but production of these growth factors in deeper layers of the synovium and the periosteum did not differ from controls. CONCLUSIONS: These results indicate the synovial macrophage to be a pivotal cell in the synovium mediating Osteophyte formation and other OA-related pathology, like fibrosis, during experimental OA. Production of growth factors and induction of synovial activation by these cells may play a crucial role in this event.
