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

Mary B. Goldring, Miguel Otero, Darren A. Plumb, Cecilia Dragomir, Marta Favero, Karim El Hachem, Ko Hashimoto, Helmtrud I. Roach, Eleonora Olivotto, Rosa Maria Borzì, Kenneth B. Marcu

Research output: Contribution to journalArticle

265 Citations (Scopus)

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 for 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 metalloproteinase (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.

Original languageEnglish
Pages (from-to)202-220
Number of pages19
JournalEuropean Cells and Materials
Volume21
DOIs
Publication statusPublished - 2011 Jan 1
Externally publishedYes

Keywords

  • BMP signaling
  • Chondrocytes
  • Collagens
  • Cytokines
  • Gene regulation

ASJC Scopus subject areas

  • Bioengineering
  • Biochemistry
  • Biomaterials
  • Biomedical Engineering
  • Cell Biology

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  • Cite this

    Goldring, M. B., Otero, M., Plumb, D. A., Dragomir, C., Favero, M., El Hachem, K., Hashimoto, K., Roach, H. I., Olivotto, E., Borzì, R. M., & Marcu, K. B. (2011). Roles of inflammatory and anabolic cytokines in cartilage metabolism: Signals and multiple effectors converge upon MMP-13 regulation in osteoarthritis. European Cells and Materials, 21, 202-220. https://doi.org/10.22203/eCM.v021a16