The Experts below are selected from a list of 327 Experts worldwide ranked by ideXlab platform
A P Hollander - One of the best experts on this subject based on the ideXlab platform.
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Type II Collagen Degradation in spontaneous osteoarthritis in C57Bl/6 and BALB/c mice.
Arthritis & Rheumatism, 1999Co-Authors: Reinout Stoop, A P Hollander, P.m. Van Der Kraan, Pieter Buma, R.c. Billinghurst, A R Poole, W.b. Van Den BergAbstract:Objective Degradation of type II Collagen during osteoarthritis (OA) is thought to be the key process leading to cartilage destruction. In this study, we investigated whether OA is characterized by either a generalized breakdown of the Collagenous network or a localized process. Furthermore, we determined if Collagen Degradation was linked to cell death. Methods Two mouse strains that develop spontaneous OA, C57Bl/6 and BALB/c mice, were examined. Type II Collagen Degradation in type II Collagen–induced arthritis was also examined for comparison. Immunolocalization with the COL2-3/4m and COL2-3/4C antibodies was used to demonstrate denatured type II Collagen and the Collagenase cleavage site in type II Collagen, respectively. Results Both the C57Bl/6 and the BALB/c mice developed OA changes, although clear compartmental differences existed between the two strains. In both strains, type II Collagen Degradation was clearly present at sites of degeneration, but was absent from intact articular cartilage. Collagen Degradation was absent from areas with cell death. Conclusion These results indicate that type II Collagen Degradation in spontaneous murine OA is associated with degeneration and is a localized, instead of a generalized, process.
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Retinoic acid–induced type II Collagen Degradation does not correlate with matrix metalloproteinase activity in cartilage explant cultures
Arthritis & Rheumatism, 1999Co-Authors: J.s. Price, L D Kozaci, Wang-weigand S, Bohne R, A P HollanderAbstract:OBJECTIVE: To determine the role of matrix metalloproteinases (MMPs) in retinoic acid (RetA)-induced Degradation of type II Collagen in cartilage. METHODS: Bovine nasal cartilage explants were cultured with 1 microM RetA or in 3 nM interleukin-1alpha (IL-1alpha). Release of proteoglycan and type II Collagen into the medium was measured by colorimetric assay and immunoassay, respectively. MMP activity in the medium was determined using a quenched fluorescent substrate assay, while specific Collagenases were identified by Western immunoblotting. In some cases the effects of low molecular mass synthetic MMP inhibitors and serum on Collagen Degradation were studied. RESULTS: RetA promoted maximal breakdown of type II Collagen after 4 or 5 weeks in culture, compared with 3 weeks in culture with IL-1alpha. In IL-1alpha-stimulated cultures, Collagen Degradation was coincident with a large increase in MMP activity in the culture medium, whereas in RetA-stimulated cultures, there was only a small increase. In Western immunoblots of culture media containing RetA, prointerstitial Collagenase and active Collagenase 3 were sometimes detected, but not in all experiments. In IL-1alpha cultures, active interstitial Collagenase was always detected, and active Collagenase 3 was detectable in some experiments. Neutrophil Collagenase was not detected in any cultures. IL-1alpha-stimulated Collagen Degradation was effectively inhibited by a potent, broad-spectrum inhibitor of MMPs, whereas it was poorly inhibited by a weak MMP inhibitor. The same 2 compounds were both only weak inhibitors of RetA-induced Collagen Degradation. When fetal calf serum was included in cartilage cultures, MMP activity in the culture medium was reduced to low levels. This resulted in a marked inhibition of IL-1alpha-induced type II Collagen Degradation, whereas there was no inhibition of RetA-induced Collagen Degradation. CONCLUSION: Unlike IL-1alpha, RetA induces Degradation of type II Collagen in cartilage explants by a mechanism that is mainly independent of those MMPs that can be detected in the culture medium.
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Denaturation of Type II Collagen in Articular Cartilage in Experimental Murine Arthritis. Evidence for Collagen Degradation in Both Reversible and Irreversible Cartilage Damage
The Journal of Pathology, 1999Co-Authors: Reinout Stoop, A P Hollander, P.m. Van Der Kraan, Pieter Buma, A R Poole, W.b. Van Den BergAbstract:Degradation of type II Collagen is thought to be a key step in the destruction of articular cartilage in patients with rheumatoid arthritis or osteoarthritis. The aim of this study was to investigate whether type II Collagen Degradation is associated with cartilage destruction. Type II Collagen Degradation was studied in two murine arthritis models, zymosan-induced arthritis (ZIA), which develops reversible articular cartilage damage based on proteoglycan analysis, and antigen-induced arthritis (AIA), in which there is irreversible damage to the cartilage. Type II Collagen Degradation was assayed immunohistochemically using the COL2-3/4m antibody which recognizes denatured type II Collagen, such as is produced by Collagenase cleavage. In both models, Degradation of type II Collagen was observed in the non-calcified articular cartilage of arthritic but not of control knees. In the patella-femoral compartment, Collagen denaturation started to increase on day 3 (ZIA) and day 7 (AIA) and remained high on day 14. In contrast, in the tibia-femoral compartment, type II Collagen breakdown was not increased before 14 days in either model. By 28 days, Collagen denaturation was strongly reduced in the patella-femoral compartment in the ZIA model, but persisted in the tibia-femoral compartment in both models. In conclusion, increased type II Collagen Degradation was found in articular cartilage of both ZIA and AIA animals. Since ZIA does not develop irreversible cartilage destruction, this indicates that cartilage may have the ability to withstand a limited degree of type II Collagen Degradation without developing irreversible damage.
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retinoic acid induced type ii Collagen Degradation does not correlate with matrix metalloproteinase activity in cartilage explant cultures
Arthritis & Rheumatism, 1999Co-Authors: J.s. Price, R Bohne, S Wangweigand, L D Kozaci, A P HollanderAbstract:OBJECTIVE: To determine the role of matrix metalloproteinases (MMPs) in retinoic acid (RetA)-induced Degradation of type II Collagen in cartilage. METHODS: Bovine nasal cartilage explants were cultured with 1 microM RetA or in 3 nM interleukin-1alpha (IL-1alpha). Release of proteoglycan and type II Collagen into the medium was measured by colorimetric assay and immunoassay, respectively. MMP activity in the medium was determined using a quenched fluorescent substrate assay, while specific Collagenases were identified by Western immunoblotting. In some cases the effects of low molecular mass synthetic MMP inhibitors and serum on Collagen Degradation were studied. RESULTS: RetA promoted maximal breakdown of type II Collagen after 4 or 5 weeks in culture, compared with 3 weeks in culture with IL-1alpha. In IL-1alpha-stimulated cultures, Collagen Degradation was coincident with a large increase in MMP activity in the culture medium, whereas in RetA-stimulated cultures, there was only a small increase. In Western immunoblots of culture media containing RetA, prointerstitial Collagenase and active Collagenase 3 were sometimes detected, but not in all experiments. In IL-1alpha cultures, active interstitial Collagenase was always detected, and active Collagenase 3 was detectable in some experiments. Neutrophil Collagenase was not detected in any cultures. IL-1alpha-stimulated Collagen Degradation was effectively inhibited by a potent, broad-spectrum inhibitor of MMPs, whereas it was poorly inhibited by a weak MMP inhibitor. The same 2 compounds were both only weak inhibitors of RetA-induced Collagen Degradation. When fetal calf serum was included in cartilage cultures, MMP activity in the culture medium was reduced to low levels. This resulted in a marked inhibition of IL-1alpha-induced type II Collagen Degradation, whereas there was no inhibition of RetA-induced Collagen Degradation. CONCLUSION: Unlike IL-1alpha, RetA induces Degradation of type II Collagen in cartilage explants by a mechanism that is mainly independent of those MMPs that can be detected in the culture medium.
Yasuhiko Masuho - One of the best experts on this subject based on the ideXlab platform.
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dexamethasone inhibits Collagen Degradation induced by the combination of interleukin 1 and plasminogen in cartilage explant culture
Biological & Pharmaceutical Bulletin, 1999Co-Authors: Shigeki Saito, Masao Katoh, Mari Masumoto, Shunichiro Matsumoto, Yasuhiko MasuhoAbstract:Glucocorticoids ameliorate erosion in animal osteoarthritis (OA) models and suppress synthesis of matrix matalloproteinases (MMP). However, in in vitro studies, their inhibitory effects on matrix Degradation of cartilage have not been well documented by monitoring aggrecan. Collagen was monitored in this study to examine the effects of dexamethasone in cartilage explant culture. Dexamethasone cleary blocked Collagen Degradation induced by the combination of interleukin-1 (IL-1) and plasminogen at the concentration of 10-9M, whcih is much lower than the concentrations reportedly required to inhibit matrix synthesis. In addition, MMP-1 and MMP-3 were suppressed by dexamethasone treatment in a similar range of concentrations. The conversion of plasminogen to plasmin, however, was not blocked by treatment with dexamethasone. These results suggest that the inhibitory effect of dexamethasone on Collagen Degradation may be due to suppression of MMP production rather than suppression of fibrinolytic cascade. Thus, the ability of glucocorticoids to inhibit matrix Degradation in vitro, which could be clearly shown by monitoring Collagen Degradation, may endorse their efficacy in animal OA models and suggest potential therapeutic effectiveness.
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involvement of mmp 1 and mmp 3 in Collagen Degradation induced by il 1 in rabbit cartilage explant culture
Life Sciences, 1998Co-Authors: Shigeki Saito, Masao Katoh, Mari Masumoto, Shunichiro Matsumoto, Yasuhiko MasuhoAbstract:Abstract To determine whether matrix metalloproteinase-1 (MMP-1) or MMP-3 is involved in cartilage Collagen Degradation, polyclonal antibodies were separately raised against MMP-1 and MMP-3 and their effects on Collagen Degradation were assessed in rabbit cartilage explant culture. We found that anti-MMP-1 antibodies completely inhibited Collagen Degradation induced by the combination of interleukin-1 (IL-1) and plasminogen. Anti-MMP-3 antibodies showed 40% inhibition at maximum concentration. These results indicate that MMP-1, and possibly MMP-3, are involved in Collagen Degradation in cartilage explant culture.
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Collagen Degradation induced by the combination of il 1α and plasminogen in rabbit articular cartilage explant culture
Journal of Biochemistry, 1997Co-Authors: Shigeki Saito, Masao Katoh, Mari Masumoto, Shunichiro Matsumoto, Yasuhiko MasuhoAbstract:: To investigate the effect of plasminogen on cartilage catabolism, we assessed Collagen Degradation in rabbit articular cartilage explants treated with or without plasminogen and interleukin-1alpha (IL-1alpha). The combination of IL-1 alpha and plasminogen induced rapid Collagen Degradation, amounting to more than 60% of the total Collagen by day 7, while neither IL-1alpha nor plasminogen alone had any effect. To examine the mechanism of Collagen Degradation induced by IL-1alpha and plasminogen, the matrix metalloproteinases (MMPs) in the culture supernatants were examined by ELISA, Western blotting and gelatin zymography. We found that the treatment with IL-1alpha induced MMP-1, MMP-3, and MMP-9. In addition, plasminogen converted the pro form of MMPs into the active form. Both a tissue inhibitor of metalloproteinases-1 (TIMP-1) and a synthetic hydroxamate MMP inhibitor prevented this Collagen release. These results suggest that plasminogen causes Collagen Degradation via activation of MMPs induced by IL-1alpha.
Shigeki Saito - One of the best experts on this subject based on the ideXlab platform.
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dexamethasone inhibits Collagen Degradation induced by the combination of interleukin 1 and plasminogen in cartilage explant culture
Biological & Pharmaceutical Bulletin, 1999Co-Authors: Shigeki Saito, Masao Katoh, Mari Masumoto, Shunichiro Matsumoto, Yasuhiko MasuhoAbstract:Glucocorticoids ameliorate erosion in animal osteoarthritis (OA) models and suppress synthesis of matrix matalloproteinases (MMP). However, in in vitro studies, their inhibitory effects on matrix Degradation of cartilage have not been well documented by monitoring aggrecan. Collagen was monitored in this study to examine the effects of dexamethasone in cartilage explant culture. Dexamethasone cleary blocked Collagen Degradation induced by the combination of interleukin-1 (IL-1) and plasminogen at the concentration of 10-9M, whcih is much lower than the concentrations reportedly required to inhibit matrix synthesis. In addition, MMP-1 and MMP-3 were suppressed by dexamethasone treatment in a similar range of concentrations. The conversion of plasminogen to plasmin, however, was not blocked by treatment with dexamethasone. These results suggest that the inhibitory effect of dexamethasone on Collagen Degradation may be due to suppression of MMP production rather than suppression of fibrinolytic cascade. Thus, the ability of glucocorticoids to inhibit matrix Degradation in vitro, which could be clearly shown by monitoring Collagen Degradation, may endorse their efficacy in animal OA models and suggest potential therapeutic effectiveness.
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involvement of mmp 1 and mmp 3 in Collagen Degradation induced by il 1 in rabbit cartilage explant culture
Life Sciences, 1998Co-Authors: Shigeki Saito, Masao Katoh, Mari Masumoto, Shunichiro Matsumoto, Yasuhiko MasuhoAbstract:Abstract To determine whether matrix metalloproteinase-1 (MMP-1) or MMP-3 is involved in cartilage Collagen Degradation, polyclonal antibodies were separately raised against MMP-1 and MMP-3 and their effects on Collagen Degradation were assessed in rabbit cartilage explant culture. We found that anti-MMP-1 antibodies completely inhibited Collagen Degradation induced by the combination of interleukin-1 (IL-1) and plasminogen. Anti-MMP-3 antibodies showed 40% inhibition at maximum concentration. These results indicate that MMP-1, and possibly MMP-3, are involved in Collagen Degradation in cartilage explant culture.
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Collagen Degradation induced by the combination of il 1α and plasminogen in rabbit articular cartilage explant culture
Journal of Biochemistry, 1997Co-Authors: Shigeki Saito, Masao Katoh, Mari Masumoto, Shunichiro Matsumoto, Yasuhiko MasuhoAbstract:: To investigate the effect of plasminogen on cartilage catabolism, we assessed Collagen Degradation in rabbit articular cartilage explants treated with or without plasminogen and interleukin-1alpha (IL-1alpha). The combination of IL-1 alpha and plasminogen induced rapid Collagen Degradation, amounting to more than 60% of the total Collagen by day 7, while neither IL-1alpha nor plasminogen alone had any effect. To examine the mechanism of Collagen Degradation induced by IL-1alpha and plasminogen, the matrix metalloproteinases (MMPs) in the culture supernatants were examined by ELISA, Western blotting and gelatin zymography. We found that the treatment with IL-1alpha induced MMP-1, MMP-3, and MMP-9. In addition, plasminogen converted the pro form of MMPs into the active form. Both a tissue inhibitor of metalloproteinases-1 (TIMP-1) and a synthetic hydroxamate MMP inhibitor prevented this Collagen release. These results suggest that plasminogen causes Collagen Degradation via activation of MMPs induced by IL-1alpha.
Pieter Buma - One of the best experts on this subject based on the ideXlab platform.
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differences in type ii Collagen Degradation between peripheral and central cartilage of rat stifle joints after cranial cruciate ligament transection
Arthritis & Rheumatism, 2000Co-Authors: Reinout Stoop, Pieter Buma, Peter M Van Der Kraan, Anthony Peter Hollander, Clark R Billinghurst, Robin A Poole, Wim B Van Den BergAbstract:Objective. Type II Collagen Degradation is thought to be the key process in cartilage Degradation during the development of osteoarthritis (OA). In this study, we investigated the kinetics of type II Collagen Degradation during surgically induced OA. Methods. Experimental OA was induced in male Wistar rats by transecting the cranial (anterior) cruciate ligament (CCL). Hematoxylin and eosin staining was used to study overall cartilage Degradation, while immunostained sections were used to demonstrate denatured type II Collagen (Col2-3/4m antibody) and the Collagenase cleavage site in type II Collagen (Col2-3/ 4Cshort antibody). Results. During the first 3‐4 weeks, cartilage destruction, associated with chondrocyte death, proteoglycan depletion, and a marked increase in the Collagenase cleavage neoepitope, was mainly located at the margins of the cartilage. From weeks 3‐4, the central part of the cartilage showed increased surface fibrillation and apparent chondrocyte death. In these areas, increased denatured type II Collagen staining but little cleavage-site staining was present. Conclusion. These results indicate that cartilage Degradation after CCL transection in the rat consists of 2 phases. An early phase located at the cartilage margins and a late phase located at the central part of the cartilage. In the early phase, Collagenase-dependent cartilage damage occurred. During the late phase, the level of type II Collagen denaturation increased.
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Type II Collagen Degradation in spontaneous osteoarthritis in C57Bl/6 and BALB/c mice.
Arthritis & Rheumatism, 1999Co-Authors: Reinout Stoop, A P Hollander, P.m. Van Der Kraan, Pieter Buma, R.c. Billinghurst, A R Poole, W.b. Van Den BergAbstract:Objective Degradation of type II Collagen during osteoarthritis (OA) is thought to be the key process leading to cartilage destruction. In this study, we investigated whether OA is characterized by either a generalized breakdown of the Collagenous network or a localized process. Furthermore, we determined if Collagen Degradation was linked to cell death. Methods Two mouse strains that develop spontaneous OA, C57Bl/6 and BALB/c mice, were examined. Type II Collagen Degradation in type II Collagen–induced arthritis was also examined for comparison. Immunolocalization with the COL2-3/4m and COL2-3/4C antibodies was used to demonstrate denatured type II Collagen and the Collagenase cleavage site in type II Collagen, respectively. Results Both the C57Bl/6 and the BALB/c mice developed OA changes, although clear compartmental differences existed between the two strains. In both strains, type II Collagen Degradation was clearly present at sites of degeneration, but was absent from intact articular cartilage. Collagen Degradation was absent from areas with cell death. Conclusion These results indicate that type II Collagen Degradation in spontaneous murine OA is associated with degeneration and is a localized, instead of a generalized, process.
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Denaturation of Type II Collagen in Articular Cartilage in Experimental Murine Arthritis. Evidence for Collagen Degradation in Both Reversible and Irreversible Cartilage Damage
The Journal of Pathology, 1999Co-Authors: Reinout Stoop, A P Hollander, P.m. Van Der Kraan, Pieter Buma, A R Poole, W.b. Van Den BergAbstract:Degradation of type II Collagen is thought to be a key step in the destruction of articular cartilage in patients with rheumatoid arthritis or osteoarthritis. The aim of this study was to investigate whether type II Collagen Degradation is associated with cartilage destruction. Type II Collagen Degradation was studied in two murine arthritis models, zymosan-induced arthritis (ZIA), which develops reversible articular cartilage damage based on proteoglycan analysis, and antigen-induced arthritis (AIA), in which there is irreversible damage to the cartilage. Type II Collagen Degradation was assayed immunohistochemically using the COL2-3/4m antibody which recognizes denatured type II Collagen, such as is produced by Collagenase cleavage. In both models, Degradation of type II Collagen was observed in the non-calcified articular cartilage of arthritic but not of control knees. In the patella-femoral compartment, Collagen denaturation started to increase on day 3 (ZIA) and day 7 (AIA) and remained high on day 14. In contrast, in the tibia-femoral compartment, type II Collagen breakdown was not increased before 14 days in either model. By 28 days, Collagen denaturation was strongly reduced in the patella-femoral compartment in the ZIA model, but persisted in the tibia-femoral compartment in both models. In conclusion, increased type II Collagen Degradation was found in articular cartilage of both ZIA and AIA animals. Since ZIA does not develop irreversible cartilage destruction, this indicates that cartilage may have the ability to withstand a limited degree of type II Collagen Degradation without developing irreversible damage.
J.s. Price - One of the best experts on this subject based on the ideXlab platform.
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Retinoic acid–induced type II Collagen Degradation does not correlate with matrix metalloproteinase activity in cartilage explant cultures
Arthritis & Rheumatism, 1999Co-Authors: J.s. Price, L D Kozaci, Wang-weigand S, Bohne R, A P HollanderAbstract:OBJECTIVE: To determine the role of matrix metalloproteinases (MMPs) in retinoic acid (RetA)-induced Degradation of type II Collagen in cartilage. METHODS: Bovine nasal cartilage explants were cultured with 1 microM RetA or in 3 nM interleukin-1alpha (IL-1alpha). Release of proteoglycan and type II Collagen into the medium was measured by colorimetric assay and immunoassay, respectively. MMP activity in the medium was determined using a quenched fluorescent substrate assay, while specific Collagenases were identified by Western immunoblotting. In some cases the effects of low molecular mass synthetic MMP inhibitors and serum on Collagen Degradation were studied. RESULTS: RetA promoted maximal breakdown of type II Collagen after 4 or 5 weeks in culture, compared with 3 weeks in culture with IL-1alpha. In IL-1alpha-stimulated cultures, Collagen Degradation was coincident with a large increase in MMP activity in the culture medium, whereas in RetA-stimulated cultures, there was only a small increase. In Western immunoblots of culture media containing RetA, prointerstitial Collagenase and active Collagenase 3 were sometimes detected, but not in all experiments. In IL-1alpha cultures, active interstitial Collagenase was always detected, and active Collagenase 3 was detectable in some experiments. Neutrophil Collagenase was not detected in any cultures. IL-1alpha-stimulated Collagen Degradation was effectively inhibited by a potent, broad-spectrum inhibitor of MMPs, whereas it was poorly inhibited by a weak MMP inhibitor. The same 2 compounds were both only weak inhibitors of RetA-induced Collagen Degradation. When fetal calf serum was included in cartilage cultures, MMP activity in the culture medium was reduced to low levels. This resulted in a marked inhibition of IL-1alpha-induced type II Collagen Degradation, whereas there was no inhibition of RetA-induced Collagen Degradation. CONCLUSION: Unlike IL-1alpha, RetA induces Degradation of type II Collagen in cartilage explants by a mechanism that is mainly independent of those MMPs that can be detected in the culture medium.
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retinoic acid induced type ii Collagen Degradation does not correlate with matrix metalloproteinase activity in cartilage explant cultures
Arthritis & Rheumatism, 1999Co-Authors: J.s. Price, R Bohne, S Wangweigand, L D Kozaci, A P HollanderAbstract:OBJECTIVE: To determine the role of matrix metalloproteinases (MMPs) in retinoic acid (RetA)-induced Degradation of type II Collagen in cartilage. METHODS: Bovine nasal cartilage explants were cultured with 1 microM RetA or in 3 nM interleukin-1alpha (IL-1alpha). Release of proteoglycan and type II Collagen into the medium was measured by colorimetric assay and immunoassay, respectively. MMP activity in the medium was determined using a quenched fluorescent substrate assay, while specific Collagenases were identified by Western immunoblotting. In some cases the effects of low molecular mass synthetic MMP inhibitors and serum on Collagen Degradation were studied. RESULTS: RetA promoted maximal breakdown of type II Collagen after 4 or 5 weeks in culture, compared with 3 weeks in culture with IL-1alpha. In IL-1alpha-stimulated cultures, Collagen Degradation was coincident with a large increase in MMP activity in the culture medium, whereas in RetA-stimulated cultures, there was only a small increase. In Western immunoblots of culture media containing RetA, prointerstitial Collagenase and active Collagenase 3 were sometimes detected, but not in all experiments. In IL-1alpha cultures, active interstitial Collagenase was always detected, and active Collagenase 3 was detectable in some experiments. Neutrophil Collagenase was not detected in any cultures. IL-1alpha-stimulated Collagen Degradation was effectively inhibited by a potent, broad-spectrum inhibitor of MMPs, whereas it was poorly inhibited by a weak MMP inhibitor. The same 2 compounds were both only weak inhibitors of RetA-induced Collagen Degradation. When fetal calf serum was included in cartilage cultures, MMP activity in the culture medium was reduced to low levels. This resulted in a marked inhibition of IL-1alpha-induced type II Collagen Degradation, whereas there was no inhibition of RetA-induced Collagen Degradation. CONCLUSION: Unlike IL-1alpha, RetA induces Degradation of type II Collagen in cartilage explants by a mechanism that is mainly independent of those MMPs that can be detected in the culture medium.