Matrilin-3 Role in Cartilage Development and Osteoarthritis

Abstract

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.

The growth plate: a physiologic overview

“…These include aggrecan, a large chondroitin sulphate proteoglycan that helps retain water in the cartilage due to its high negative ionic charge. 10 Matrillins help hold aggrecan clumps in place, 11 whereas perlecan, a large heparin sulphate/chondroitin sulphate complex, helps provide structural strength and promotes angiogenesis. 12 Cartilage oligomeric matrix protein, also known as COMP5 or thrombospondin5, provides homeostatic support for the chondrocytes themselves and catalyses the polymerization of type II collagen.…”

Matrilin‐3 codelivery with adipose‐derived mesenchymal stem cells promotes articular cartilage regeneration in a rat osteochondral defect model

“…The results of several recent studies suggest that combining MSCs with chemical agents or platelet lysates yields articular cartilage with improved quality (Bornes et al, 2014;Filardo et al, 2013;Lee et al, 2014). Besides chemical agents or platelet lysates, matrilin-3 is considered a potential molecule for codelivery with MSCs (Muttigi, Han, Park, Park, & Lee, 2016).…”

Overexpression of MATN3 predicts poor prognosis of gastric adenocarcinoma: based on TCGA database

“…In primary human chondrocytes, MATN3 can induce the expression of MMP1, MMP3, MMP13, and COX2, indicating that MATN3 can regulate extracellular matrix degradation [12]. Existing data [13,14] provide insights into the critical role of matrilin-3 in in ammation, matrix degradation, and matrix formation in cartilage development and osteoarthritis. So far, although many studies about MATN3 have been limited to epiphyseal disease, few studies have been reported on other conditions such as malignant tumors.…”