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A Molecular Cascade Underlying Articular Cartilage Degeneration

[ Vol. 21 , Issue. 9 ]

Author(s):

Lin Xu and Yefu Li*   Pages 838 - 848 ( 11 )

Abstract:


Preserving of articular cartilage is an effective way to protect synovial joints from becoming osteoarthritic (OA) joints. Understanding of the molecular basis of articular cartilage degeneration will provide valuable information in the effort to develop cartilage preserving drugs. There are currently no disease-modifying OA drugs (DMOADs) available to prevent articular cartilage destruction during the development of OA. Current drug treatments for OA focus on the reduction of joint pain, swelling, and inflammation at advanced stages of the disease. However, based on discoveries from several independent research laboratories and our laboratory in the past 15 to 20 years, we believe that we have a functional molecular understanding of articular cartilage degeneration. In this review article, we present and discuss experimental evidence to demonstrate a sequential chain of the molecular events underlying articular cartilage degeneration, which consists of transforming growth factor beta 1, high-temperature requirement A1 (a serine protease), discoidin domain receptor 2 (a cell surface receptor tyrosine kinase for native fibrillar collagens), and matrix metalloproteinase 13 (an extracellularmatrix degrading enzyme). If, as we strongly suspect, this molecular pathway is responsible for the initiation and acceleration of articular cartilage degeneration, which eventually leads to progressive joint failure, then these molecules may be ideal therapeutic targets for the development of DMOADs.

Keywords:

TGF-β1, HTRA1, DDR2, MMP-13, articular cartilage, degeneration, osteoarthritis.

Affiliation:

Department of Developmental Biology, Harvard School of Dental Medicine, 188 Longwood Ave. Boston, MA 02115 & Faculty of Medicine, Harvard Medical School 25 Shattuck St. Boston, MA 02115, Department of Developmental Biology, Harvard School of Dental Medicine, 188 Longwood Ave. Boston, MA 02115 & Faculty of Medicine, Harvard Medical School 25 Shattuck St. Boston, MA 02115

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