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ISSN 1473-2262   NLM: 100973416 (link) The leading Journal of musculoskeletal research.
 

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2011   Volume No 21 – pages 202-220

Title: Roles of inflammatory and anabolic cytokines in cartilage metabolism: signals and multiple effectors converge upon MMP-13 regulation in osteoarthritis

Author: MB Goldring, M Otero, DA Plumb, C Dragomir, M Favero, K El Hachem, K Hashimoto, HI Roach, E Olivotto, RM Borzì, KB Marcu

Address: 535 East 70th Street, Caspary Research Building, 5th Floor, New York, NY 10021, USA

E-mail: goldringm at hss.edu

Key Words: Chondrocytes, gene Regulation, cytokines, BMP signaling, collagens.

Publication date: February 24th 2011

Abstract: Human cartilage is a complex tissue of matrix proteins that vary in amount and orientation from superficial to deep layers and from loaded to unloaded zones. A major challenge to efforts to repair cartilage by stem cell-based and other tissue engineering strategies is the inability of the resident chondrocytes to lay down new matrix with the same structural and resilient properties that it had upon its original formation. This is particularly true of the collagen network, which is susceptible to cleavage once proteoglycans are depleted. Thus, a thorough understanding of the similarities and particularly the marked differences in mechanisms of cartilage remodeling during development, osteoarthritis, and aging may lead to more effective strategies for preventing cartilage damage and promoting repair. To identify and characterize effectors or regulators of cartilage remodeling in these processes, we are using culture models of primary human and mouse chondrocytes and cell lines and mouse genetic models to manipulate gene expression programs leading to matrix remodeling and subsequent chondrocyte hypertrophic differentiation, pivotal processes which both go astray in OA disease. Matrix metalloproteinases (MMP)-13, the major type II collagen-degrading collagenase, is regulated by stress-, inflammation-, and differentiation-induced signals that not only contribute to irreversible joint damage (progression) in OA, but importantly, also to the initiation/onset phase, wherein chondrocytes in articular cartilage leave their natural growth- and differentiation-arrested state. Our work points to common mediators of these processes in human OA cartilage and in early through late stages of OA in surgical and genetic mouse models.

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Last modified February 26, 2013

Open Access / Author retains copyright

AO Foundation, Davos, Switzerland