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Int. J. Mol. Sci. 2016, 17(4), 590;

Matrilin-3 Role in Cartilage Development and Osteoarthritis

School of Integrative Engineering, Chung-Ang University, Seoul 06911, Korea
Department of Biomedical Science, CHA University, Seongnam-Si 13488, Korea
Department of Neurosurgery, CHA Bundang Medical Center, CHA University, Seongnam-si 13496, Korea
Department of Biomedical Engineering, Collage of Medicine, Kyung Hee University, Seoul 02447, Korea
Authors to whom correspondence should be addressed.
Academic Editor: Ge Zhang
Received: 19 February 2016 / Revised: 10 April 2016 / Accepted: 13 April 2016 / Published: 20 April 2016
(This article belongs to the Special Issue Translational Molecular Medicine & Molecular Drug Discovery)
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The extracellular matrix (ECM) of cartilage performs essential functions in differentiation and chondroprogenitor cell maintenance during development and regeneration. Here, we discuss the vital role of matrilin-3, an ECM protein involved in cartilage development and potential osteoarthritis pathomechanisms. As an adaptor protein, matrilin-3 binds to collagen IX to form a filamentous network around cells. Matrilin-3 is an essential component during cartilage development and ossification. In addition, it interacts directly or indirectly with transforming growth factor β (TGF-β), and bone morphogenetic protein 2 (BMP2) eventually regulates chondrocyte proliferation and hypertrophic differentiation. Interestingly, matrilin-3 increases interleukin receptor antagonists (IL-Ra) in chondrocytes, suggesting its role in the suppression of IL-1β-mediated inflammatory action. Matrilin-3 downregulates the expression of matrix-degrading enzymes, such as a disintegrin metalloproteinase with thrombospondin motifs 4 (ADAMTS4) and ADAMTS5, matrix metalloproteinase 13 (MMP13), and collagen X, a hypertrophy marker during development and inflammatory conditions. Matrilin-3 essentially enhances collagen II and aggrecan expression, which are required to maintain the tensile strength and elasticity of cartilage, respectively. Interestingly, despite these attributes, matrilin-3 induces osteoarthritis-associated markers in chondrocytes in a concentration-dependent manner. Existing data provide insights into the critical role of matrilin-3 in inflammation, matrix degradation, and matrix formation in cartilage development and osteoarthritis. View Full-Text
Keywords: matrilin-3; extracellular matrix; cartilage; hypertrophy; interleukin receptor antagonist; osteoarthritis matrilin-3; extracellular matrix; cartilage; hypertrophy; interleukin receptor antagonist; osteoarthritis

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Muttigi, M.S.; Han, I.; Park, H.-K.; Park, H.; Lee, S.-H. Matrilin-3 Role in Cartilage Development and Osteoarthritis. Int. J. Mol. Sci. 2016, 17, 590.

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