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Klaus Wielckens - One of the best experts on this subject based on the ideXlab platform.
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a critical role for collagen ii in Cartilage Matrix degradation collagen ii induces pro inflammatory cytokines and mmps in primary human chondrocytes
Journal of Orthopaedic Research, 2009Co-Authors: Andreas R Klatt, Gabriele Klinger, Joerg H. Renno, Gebhart Malchau, Brigitte Paulklausch, Getrud Kuhn, Marc Banerjee, Klaus WielckensAbstract:We report a process that results in the acceleration of Matrix degradation in human articular Cartilage, a phenomenon commonly observed in osteoarthritis (OA). The study was conducted by (1) examining the potential of collagen II in modulating the gene expression profile of primary human chondrocytes (PHCs), and (2) investigating the involvement of pro-inflammatory signaling cascades. We first tested the collagen II-dependent induction of pro-inflammatory cytokines and Matrix metalloproteinases (MMPs) in PHCs. PHCs were incubated with or without monomeric (i.e., nonfibrillar) collagen II. Cells were then analyzed by RT-PCR for the expression of MMP1, MMP3, MMP13, MMP14, and IL-1β. ELISA was used to quantify IL-6 and IL-8 release. To examine the influence of collagen II signaling, specifically the role of MAPK p38, a p38-inhibitor was added prior to collagen treatment. Changes in IκB concentration were monitored by immunoblot analysis to detect NFκB signaling. Results indicated that incubation of PHCs with collagen II did produce a dose-dependent induction of MMP1, MMP3, MMP13, MMP14, as well as cytokines IL-1β, IL-6, and IL-8. At the same time, inhibition of p38 and IκB degradation revealed that collagen II-dependent gene induction also involves MAPK p38 and NFκB signaling. Thus, we provide evidence for a collagen II-dependent feed-forward mechanism whereby collagen II induces first MMPs and pro-inflammatory cytokines and then release of collagen II fragments from mature collagen II fibers. This, in turn, induces more pro-inflammatory cytokines and MMPs, and the process is repeated, which results in the acceleration and perpetuation of Cartilage Matrix degradation. © 2008 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 27:65–70, 2009
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a critical role for collagen ii in Cartilage Matrix degradation collagen ii induces pro inflammatory cytokines and mmps in primary human chondrocytes
Journal of Orthopaedic Research, 2009Co-Authors: Andreas R Klatt, Gabriele Klinger, Joerg H. Renno, Gebhart Malchau, Brigitte Paulklausch, Getrud Kuhn, Marc Banerjee, Klaus WielckensAbstract:We report a process that results in the acceleration of Matrix degradation in human articular Cartilage, a phenomenon commonly observed in osteoarthritis (OA). The study was conducted by (1) examining the potential of collagen II in modulating the gene expression profile of primary human chondrocytes (PHCs), and (2) investigating the involvement of pro-inflammatory signaling cascades. We first tested the collagen II-dependent induction of pro-inflammatory cytokines and Matrix metalloproteinases (MMPs) in PHCs. PHCs were incubated with or without monomeric (i.e., nonfibrillar) collagen II. Cells were then analyzed by RT-PCR for the expression of MMP1, MMP3, MMP13, MMP14, and IL-1beta. ELISA was used to quantify IL-6 and IL-8 release. To examine the influence of collagen II signaling, specifically the role of MAPK p38, a p38-inhibitor was added prior to collagen treatment. Changes in IkappaB concentration were monitored by immunoblot analysis to detect NFkappaB signaling. Results indicated that incubation of PHCs with collagen II did produce a dose-dependent induction of MMP1, MMP3, MMP13, MMP14, as well as cytokines IL-1beta, IL-6, and IL-8. At the same time, inhibition of p38 and IkappaB degradation revealed that collagen II-dependent gene induction also involves MAPK p38 and NFkappaB signaling. Thus, we provide evidence for a collagen II-dependent feed-forward mechanism whereby collagen II induces first MMPs and pro-inflammatory cytokines and then release of collagen II fragments from mature collagen II fibers. This, in turn, induces more pro-inflammatory cytokines and MMPs, and the process is repeated, which results in the acceleration and perpetuation of Cartilage Matrix degradation.
Andreas R Klatt - One of the best experts on this subject based on the ideXlab platform.
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a critical role for collagen ii in Cartilage Matrix degradation collagen ii induces pro inflammatory cytokines and mmps in primary human chondrocytes
Journal of Orthopaedic Research, 2009Co-Authors: Andreas R Klatt, Gabriele Klinger, Joerg H. Renno, Gebhart Malchau, Brigitte Paulklausch, Getrud Kuhn, Marc Banerjee, Klaus WielckensAbstract:We report a process that results in the acceleration of Matrix degradation in human articular Cartilage, a phenomenon commonly observed in osteoarthritis (OA). The study was conducted by (1) examining the potential of collagen II in modulating the gene expression profile of primary human chondrocytes (PHCs), and (2) investigating the involvement of pro-inflammatory signaling cascades. We first tested the collagen II-dependent induction of pro-inflammatory cytokines and Matrix metalloproteinases (MMPs) in PHCs. PHCs were incubated with or without monomeric (i.e., nonfibrillar) collagen II. Cells were then analyzed by RT-PCR for the expression of MMP1, MMP3, MMP13, MMP14, and IL-1beta. ELISA was used to quantify IL-6 and IL-8 release. To examine the influence of collagen II signaling, specifically the role of MAPK p38, a p38-inhibitor was added prior to collagen treatment. Changes in IkappaB concentration were monitored by immunoblot analysis to detect NFkappaB signaling. Results indicated that incubation of PHCs with collagen II did produce a dose-dependent induction of MMP1, MMP3, MMP13, MMP14, as well as cytokines IL-1beta, IL-6, and IL-8. At the same time, inhibition of p38 and IkappaB degradation revealed that collagen II-dependent gene induction also involves MAPK p38 and NFkappaB signaling. Thus, we provide evidence for a collagen II-dependent feed-forward mechanism whereby collagen II induces first MMPs and pro-inflammatory cytokines and then release of collagen II fragments from mature collagen II fibers. This, in turn, induces more pro-inflammatory cytokines and MMPs, and the process is repeated, which results in the acceleration and perpetuation of Cartilage Matrix degradation.
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a critical role for collagen ii in Cartilage Matrix degradation collagen ii induces pro inflammatory cytokines and mmps in primary human chondrocytes
Journal of Orthopaedic Research, 2009Co-Authors: Andreas R Klatt, Gabriele Klinger, Joerg H. Renno, Gebhart Malchau, Brigitte Paulklausch, Getrud Kuhn, Marc Banerjee, Klaus WielckensAbstract:We report a process that results in the acceleration of Matrix degradation in human articular Cartilage, a phenomenon commonly observed in osteoarthritis (OA). The study was conducted by (1) examining the potential of collagen II in modulating the gene expression profile of primary human chondrocytes (PHCs), and (2) investigating the involvement of pro-inflammatory signaling cascades. We first tested the collagen II-dependent induction of pro-inflammatory cytokines and Matrix metalloproteinases (MMPs) in PHCs. PHCs were incubated with or without monomeric (i.e., nonfibrillar) collagen II. Cells were then analyzed by RT-PCR for the expression of MMP1, MMP3, MMP13, MMP14, and IL-1β. ELISA was used to quantify IL-6 and IL-8 release. To examine the influence of collagen II signaling, specifically the role of MAPK p38, a p38-inhibitor was added prior to collagen treatment. Changes in IκB concentration were monitored by immunoblot analysis to detect NFκB signaling. Results indicated that incubation of PHCs with collagen II did produce a dose-dependent induction of MMP1, MMP3, MMP13, MMP14, as well as cytokines IL-1β, IL-6, and IL-8. At the same time, inhibition of p38 and IκB degradation revealed that collagen II-dependent gene induction also involves MAPK p38 and NFκB signaling. Thus, we provide evidence for a collagen II-dependent feed-forward mechanism whereby collagen II induces first MMPs and pro-inflammatory cytokines and then release of collagen II fragments from mature collagen II fibers. This, in turn, induces more pro-inflammatory cytokines and MMPs, and the process is repeated, which results in the acceleration and perpetuation of Cartilage Matrix degradation. © 2008 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 27:65–70, 2009
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Matrilin-3 in human articular Cartilage: increased expression in osteoarthritis.
Osteoarthritis and cartilage, 2002Co-Authors: O. Pullig, Raimund Wagener, Andreas R Klatt, G. Weseloh, Bernd SwobodaAbstract:Abstract Objective Matrilin-3 is a member of the recently described matrilin family of extracellular Matrix proteins containing von Willebrand factor A-like domains. The matrilin-3 subunit can form homo-tetramers as well as hetero-oligomers together with subunits of matrilin-1 (Cartilage Matrix protein). It has a restricted tissue distribution and is strongly expressed in growing skeletal tissues. Detailed information on expression and distribution of extracellular Matrix proteins is important to understand Cartilage function in health and in disease like osteoarthritis (OA). Methods Normal and osteoarthritic Cartilage were systematically analysed for matrilin-3 expression, using immunohistochemistry, Western blot analysis, in situ hybridization, and quantitative PCR. Results Our results indicate that matrilin-3 is a mandatory component of mature articular Cartilage with its expression being restricted to chondrocytes from the tangential zone and the upper middle Cartilage zone. Osteoarthritic Cartilage samples with only moderate morphological osteoarthritic degenerations have elevated levels of matrilin-3 mRNA. In parallel, we found an increased deposition of matrilin-3 protein in the Cartilage Matrix. Matrilin-3 staining was diffusely distributed in the Cartilage Matrix, with no cellular staining being detectable. In Cartilage samples with minor osteoarthritic lesions, matrilin-3 deposition was restricted to the middle zone and to the upper deep zone. A strong correlation was found between enhanced matrilin-3 gene and protein expression and the extent of tissue damage. Sections with severe osteoarthritic degeneration showed the highest amount of matrilin-3 mRNA, strong signals in in situ hybridization, and prominent protein deposition in the middle and deep Cartilage zone. Conclusion We conclude that matrilin-3 is an integral component of human articular Cartilage Matrix and that the enhanced expression of matrilin-3 in OA may be a cellular response to the modified microenvironment in the disease.
Philippe Galera - One of the best experts on this subject based on the ideXlab platform.
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enhanced hyaline Cartilage Matrix synthesis in collagen sponge scaffolds by using sirna to stabilize chondrocytes phenotype cultured with bone morphogenetic protein 2 under hypoxia
Tissue Engineering Part C-methods, 2013Co-Authors: Florence Legendre, David Ollitrault, Magalie Hervieu, Catherine Bauge, Laure Maneix, Didier Goux, Hanane Chajra, Frederic Malleingerin, Karim Boumediene, Philippe GaleraAbstract:Cartilage healing by tissue engineering is an alternative strategy to reconstitute functional tissue after trauma or age-related degeneration. However, chondrocytes, the major player in Cartilage homeostasis, do not self-regenerate efficiently and lose their phenotype during osteoarthritis. This process is called dedifferentiation and also occurs during the first expansion step of autologous chondrocyte implantation (ACI). To ensure successful ACI therapy, chondrocytes must be differentiated and capable of synthesizing hyaline Cartilage Matrix molecules. We therefore developed a safe procedure for redifferentiating human chondrocytes by combining appropriate physicochemical factors: hypoxic conditions, collagen scaffolds, chondrogenic factors (bone morphogenetic protein-2 [BMP-2], and insulin-like growth factor I [IGF-I]) and RNA interference targeting the COL1A1 gene. Redifferentiation of dedifferentiated chondrocytes was evaluated using gene/protein analyses to identify the chondrocyte phenotypic profil...
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enhanced hyaline Cartilage Matrix synthesis in collagen sponge scaffolds by using sirna to stabilize chondrocytes phenotype cultured with bone morphogenetic protein 2 under hypoxia
Tissue Engineering Part C-methods, 2013Co-Authors: Florence Legendre, David Ollitrault, Magalie Hervieu, Catherine Bauge, Laure Maneix, Didier Goux, Hanane Chajra, Frederic Malleingerin, Karim Boumediene, Philippe GaleraAbstract:Cartilage healing by tissue engineering is an alternative strategy to reconstitute functional tissue after trauma or age-related degeneration. However, chondrocytes, the major player in Cartilage homeostasis, do not self-regenerate efficiently and lose their phenotype during osteoarthritis. This process is called dedifferentiation and also occurs during the first expansion step of autologous chondrocyte implantation (ACI). To ensure successful ACI therapy, chondrocytes must be differentiated and capable of synthesizing hyaline Cartilage Matrix molecules. We therefore developed a safe procedure for redifferentiating human chondrocytes by combining appropriate physicochemical factors: hypoxic conditions, collagen scaffolds, chondrogenic factors (bone morphogenetic protein-2 [BMP-2], and insulin-like growth factor I [IGF-I]) and RNA interference targeting the COL1A1 gene. Redifferentiation of dedifferentiated chondrocytes was evaluated using gene/protein analyses to identify the chondrocyte phenotypic profile. In our conditions, under BMP-2 treatment, redifferentiated and metabolically active chondrocytes synthesized a hyaline-like Cartilage Matrix characterized by type IIB collagen and aggrecan molecules without any sign of hypertrophy or osteogenesis. In contrast, IGF-I increased both specific and noncharacteristic markers (collagens I and X) of chondrocytes. The specific increase in COL2A1 gene expression observed in the BMP-2 treatment was shown to involve the specific enhancer region of COL2A1 that binds the trans-activators Sox9/L-Sox5/Sox6 and Sp1, which are associated with a decrease in the trans-inhibitors of COL2A1, c-Krox, and p65 subunit of NF-kappaB. Our procedure in which BMP-2 treatment under hypoxia is associated with a COL1A1 siRNA, significantly increased the differentiation index of chondrocytes, and should offer the opportunity to develop new ACI-based therapies in humans.
Florence Legendre - One of the best experts on this subject based on the ideXlab platform.
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enhanced hyaline Cartilage Matrix synthesis in collagen sponge scaffolds by using sirna to stabilize chondrocytes phenotype cultured with bone morphogenetic protein 2 under hypoxia
Tissue Engineering Part C-methods, 2013Co-Authors: Florence Legendre, David Ollitrault, Magalie Hervieu, Catherine Bauge, Laure Maneix, Didier Goux, Hanane Chajra, Frederic Malleingerin, Karim Boumediene, Philippe GaleraAbstract:Cartilage healing by tissue engineering is an alternative strategy to reconstitute functional tissue after trauma or age-related degeneration. However, chondrocytes, the major player in Cartilage homeostasis, do not self-regenerate efficiently and lose their phenotype during osteoarthritis. This process is called dedifferentiation and also occurs during the first expansion step of autologous chondrocyte implantation (ACI). To ensure successful ACI therapy, chondrocytes must be differentiated and capable of synthesizing hyaline Cartilage Matrix molecules. We therefore developed a safe procedure for redifferentiating human chondrocytes by combining appropriate physicochemical factors: hypoxic conditions, collagen scaffolds, chondrogenic factors (bone morphogenetic protein-2 [BMP-2], and insulin-like growth factor I [IGF-I]) and RNA interference targeting the COL1A1 gene. Redifferentiation of dedifferentiated chondrocytes was evaluated using gene/protein analyses to identify the chondrocyte phenotypic profil...
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enhanced hyaline Cartilage Matrix synthesis in collagen sponge scaffolds by using sirna to stabilize chondrocytes phenotype cultured with bone morphogenetic protein 2 under hypoxia
Tissue Engineering Part C-methods, 2013Co-Authors: Florence Legendre, David Ollitrault, Magalie Hervieu, Catherine Bauge, Laure Maneix, Didier Goux, Hanane Chajra, Frederic Malleingerin, Karim Boumediene, Philippe GaleraAbstract:Cartilage healing by tissue engineering is an alternative strategy to reconstitute functional tissue after trauma or age-related degeneration. However, chondrocytes, the major player in Cartilage homeostasis, do not self-regenerate efficiently and lose their phenotype during osteoarthritis. This process is called dedifferentiation and also occurs during the first expansion step of autologous chondrocyte implantation (ACI). To ensure successful ACI therapy, chondrocytes must be differentiated and capable of synthesizing hyaline Cartilage Matrix molecules. We therefore developed a safe procedure for redifferentiating human chondrocytes by combining appropriate physicochemical factors: hypoxic conditions, collagen scaffolds, chondrogenic factors (bone morphogenetic protein-2 [BMP-2], and insulin-like growth factor I [IGF-I]) and RNA interference targeting the COL1A1 gene. Redifferentiation of dedifferentiated chondrocytes was evaluated using gene/protein analyses to identify the chondrocyte phenotypic profile. In our conditions, under BMP-2 treatment, redifferentiated and metabolically active chondrocytes synthesized a hyaline-like Cartilage Matrix characterized by type IIB collagen and aggrecan molecules without any sign of hypertrophy or osteogenesis. In contrast, IGF-I increased both specific and noncharacteristic markers (collagens I and X) of chondrocytes. The specific increase in COL2A1 gene expression observed in the BMP-2 treatment was shown to involve the specific enhancer region of COL2A1 that binds the trans-activators Sox9/L-Sox5/Sox6 and Sp1, which are associated with a decrease in the trans-inhibitors of COL2A1, c-Krox, and p65 subunit of NF-kappaB. Our procedure in which BMP-2 treatment under hypoxia is associated with a COL1A1 siRNA, significantly increased the differentiation index of chondrocytes, and should offer the opportunity to develop new ACI-based therapies in humans.
Joerg H. Renno - One of the best experts on this subject based on the ideXlab platform.
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a critical role for collagen ii in Cartilage Matrix degradation collagen ii induces pro inflammatory cytokines and mmps in primary human chondrocytes
Journal of Orthopaedic Research, 2009Co-Authors: Andreas R Klatt, Gabriele Klinger, Joerg H. Renno, Gebhart Malchau, Brigitte Paulklausch, Getrud Kuhn, Marc Banerjee, Klaus WielckensAbstract:We report a process that results in the acceleration of Matrix degradation in human articular Cartilage, a phenomenon commonly observed in osteoarthritis (OA). The study was conducted by (1) examining the potential of collagen II in modulating the gene expression profile of primary human chondrocytes (PHCs), and (2) investigating the involvement of pro-inflammatory signaling cascades. We first tested the collagen II-dependent induction of pro-inflammatory cytokines and Matrix metalloproteinases (MMPs) in PHCs. PHCs were incubated with or without monomeric (i.e., nonfibrillar) collagen II. Cells were then analyzed by RT-PCR for the expression of MMP1, MMP3, MMP13, MMP14, and IL-1β. ELISA was used to quantify IL-6 and IL-8 release. To examine the influence of collagen II signaling, specifically the role of MAPK p38, a p38-inhibitor was added prior to collagen treatment. Changes in IκB concentration were monitored by immunoblot analysis to detect NFκB signaling. Results indicated that incubation of PHCs with collagen II did produce a dose-dependent induction of MMP1, MMP3, MMP13, MMP14, as well as cytokines IL-1β, IL-6, and IL-8. At the same time, inhibition of p38 and IκB degradation revealed that collagen II-dependent gene induction also involves MAPK p38 and NFκB signaling. Thus, we provide evidence for a collagen II-dependent feed-forward mechanism whereby collagen II induces first MMPs and pro-inflammatory cytokines and then release of collagen II fragments from mature collagen II fibers. This, in turn, induces more pro-inflammatory cytokines and MMPs, and the process is repeated, which results in the acceleration and perpetuation of Cartilage Matrix degradation. © 2008 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 27:65–70, 2009
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a critical role for collagen ii in Cartilage Matrix degradation collagen ii induces pro inflammatory cytokines and mmps in primary human chondrocytes
Journal of Orthopaedic Research, 2009Co-Authors: Andreas R Klatt, Gabriele Klinger, Joerg H. Renno, Gebhart Malchau, Brigitte Paulklausch, Getrud Kuhn, Marc Banerjee, Klaus WielckensAbstract:We report a process that results in the acceleration of Matrix degradation in human articular Cartilage, a phenomenon commonly observed in osteoarthritis (OA). The study was conducted by (1) examining the potential of collagen II in modulating the gene expression profile of primary human chondrocytes (PHCs), and (2) investigating the involvement of pro-inflammatory signaling cascades. We first tested the collagen II-dependent induction of pro-inflammatory cytokines and Matrix metalloproteinases (MMPs) in PHCs. PHCs were incubated with or without monomeric (i.e., nonfibrillar) collagen II. Cells were then analyzed by RT-PCR for the expression of MMP1, MMP3, MMP13, MMP14, and IL-1beta. ELISA was used to quantify IL-6 and IL-8 release. To examine the influence of collagen II signaling, specifically the role of MAPK p38, a p38-inhibitor was added prior to collagen treatment. Changes in IkappaB concentration were monitored by immunoblot analysis to detect NFkappaB signaling. Results indicated that incubation of PHCs with collagen II did produce a dose-dependent induction of MMP1, MMP3, MMP13, MMP14, as well as cytokines IL-1beta, IL-6, and IL-8. At the same time, inhibition of p38 and IkappaB degradation revealed that collagen II-dependent gene induction also involves MAPK p38 and NFkappaB signaling. Thus, we provide evidence for a collagen II-dependent feed-forward mechanism whereby collagen II induces first MMPs and pro-inflammatory cytokines and then release of collagen II fragments from mature collagen II fibers. This, in turn, induces more pro-inflammatory cytokines and MMPs, and the process is repeated, which results in the acceleration and perpetuation of Cartilage Matrix degradation.