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Klaus Wielckens - One of the best experts on this subject based on the ideXlab platform.
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matrilin 3 activates the expression of osteoarthritis associated genes in primary human chondrocytes
FEBS Letters, 2009Co-Authors: Andreas R Klatt, Mats Paulsson, Raimund Wagener, Gabriele Klinger, Gertrud Kühn, Joerg H. Renno, Joachim Schmidt, Gebhart Malchau, Brigitte Paulklausch, Klaus WielckensAbstract:Here, we tested the matrilin-3-dependent induction of osteoarthritis-associated genes in primary human chondrocytes. Matrilin stimulation leads to the induction of MMP1, MMP3, MMP13, COX-2, iNOS, IL-1β, TNFα, IL-6 and IL-8. Furthermore, we show the participation of ADAMTS4 and ADAMTS5 in the in vitro degradation of matrilin-3. We provide evidence for a matrilin-3-dependent feed-forward mechanism of matrix degradation, whereby proteolytically-released matrilin-3 induces pro-inflammatory cytokines as well as ADAMTS4 and -5 indirectly via IL-1β. ADAMTS4 and ADAMTS5, in turn, cleave matrilin-3 and may release more matrilin-3 from the matrix, which could lead to further release of pro-inflammatory cytokines and proteases in cartilage.
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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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matrilin 3 activates the expression of osteoarthritis associated genes in primary human chondrocytes
FEBS Letters, 2009Co-Authors: Andreas R Klatt, Mats Paulsson, Raimund Wagener, Gabriele Klinger, Gertrud Kühn, Joerg H. Renno, Joachim Schmidt, Gebhart Malchau, Brigitte Paulklausch, Klaus WielckensAbstract:Here, we tested the matrilin-3-dependent induction of osteoarthritis-associated genes in primary human chondrocytes. Matrilin stimulation leads to the induction of MMP1, MMP3, MMP13, COX-2, iNOS, IL-1β, TNFα, IL-6 and IL-8. Furthermore, we show the participation of ADAMTS4 and ADAMTS5 in the in vitro degradation of matrilin-3. We provide evidence for a matrilin-3-dependent feed-forward mechanism of matrix degradation, whereby proteolytically-released matrilin-3 induces pro-inflammatory cytokines as well as ADAMTS4 and -5 indirectly via IL-1β. ADAMTS4 and ADAMTS5, in turn, cleave matrilin-3 and may release more matrilin-3 from the matrix, which could lead to further release of pro-inflammatory cytokines and proteases in cartilage.
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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.
Gabriele Klinger - One of the best experts on this subject based on the ideXlab platform.
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matrilin 3 activates the expression of osteoarthritis associated genes in primary human chondrocytes
FEBS Letters, 2009Co-Authors: Andreas R Klatt, Mats Paulsson, Raimund Wagener, Gabriele Klinger, Gertrud Kühn, Joerg H. Renno, Joachim Schmidt, Gebhart Malchau, Brigitte Paulklausch, Klaus WielckensAbstract:Here, we tested the matrilin-3-dependent induction of osteoarthritis-associated genes in primary human chondrocytes. Matrilin stimulation leads to the induction of MMP1, MMP3, MMP13, COX-2, iNOS, IL-1β, TNFα, IL-6 and IL-8. Furthermore, we show the participation of ADAMTS4 and ADAMTS5 in the in vitro degradation of matrilin-3. We provide evidence for a matrilin-3-dependent feed-forward mechanism of matrix degradation, whereby proteolytically-released matrilin-3 induces pro-inflammatory cytokines as well as ADAMTS4 and -5 indirectly via IL-1β. ADAMTS4 and ADAMTS5, in turn, cleave matrilin-3 and may release more matrilin-3 from the matrix, which could lead to further release of pro-inflammatory cytokines and proteases in cartilage.
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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.
Brigitte Paulklausch - One of the best experts on this subject based on the ideXlab platform.
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matrilin 3 activates the expression of osteoarthritis associated genes in primary human chondrocytes
FEBS Letters, 2009Co-Authors: Andreas R Klatt, Mats Paulsson, Raimund Wagener, Gabriele Klinger, Gertrud Kühn, Joerg H. Renno, Joachim Schmidt, Gebhart Malchau, Brigitte Paulklausch, Klaus WielckensAbstract:Here, we tested the matrilin-3-dependent induction of osteoarthritis-associated genes in primary human chondrocytes. Matrilin stimulation leads to the induction of MMP1, MMP3, MMP13, COX-2, iNOS, IL-1β, TNFα, IL-6 and IL-8. Furthermore, we show the participation of ADAMTS4 and ADAMTS5 in the in vitro degradation of matrilin-3. We provide evidence for a matrilin-3-dependent feed-forward mechanism of matrix degradation, whereby proteolytically-released matrilin-3 induces pro-inflammatory cytokines as well as ADAMTS4 and -5 indirectly via IL-1β. ADAMTS4 and ADAMTS5, in turn, cleave matrilin-3 and may release more matrilin-3 from the matrix, which could lead to further release of pro-inflammatory cytokines and proteases in cartilage.
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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.
Gebhart Malchau - One of the best experts on this subject based on the ideXlab platform.
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matrilin 3 activates the expression of osteoarthritis associated genes in primary human chondrocytes
FEBS Letters, 2009Co-Authors: Andreas R Klatt, Mats Paulsson, Raimund Wagener, Gabriele Klinger, Gertrud Kühn, Joerg H. Renno, Joachim Schmidt, Gebhart Malchau, Brigitte Paulklausch, Klaus WielckensAbstract:Here, we tested the matrilin-3-dependent induction of osteoarthritis-associated genes in primary human chondrocytes. Matrilin stimulation leads to the induction of MMP1, MMP3, MMP13, COX-2, iNOS, IL-1β, TNFα, IL-6 and IL-8. Furthermore, we show the participation of ADAMTS4 and ADAMTS5 in the in vitro degradation of matrilin-3. We provide evidence for a matrilin-3-dependent feed-forward mechanism of matrix degradation, whereby proteolytically-released matrilin-3 induces pro-inflammatory cytokines as well as ADAMTS4 and -5 indirectly via IL-1β. ADAMTS4 and ADAMTS5, in turn, cleave matrilin-3 and may release more matrilin-3 from the matrix, which could lead to further release of pro-inflammatory cytokines and proteases in cartilage.
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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.