Matrilin-3

Matrilin-3 is a non-collagenous extracellular matrix (ECM) protein that plays a crucial role in the structural integrity and function of cartilage. It is part of the matrilin family, which consists of four known members, each with distinct structural characteristics and tissue distribution. Matrilin-3, encoded by the MATN3 gene, is predominantly expressed in cartilage and is involved in the formation of filamentous networks that are essential for the mechanical properties of cartilage.

Structure

Matrilin-3 is a modular protein composed of one von Willebrand factor A (vWA) domain, four epidermal growth factor (EGF)-like domains, and a single coiled-coil domain. This structure facilitates its role in mediating cell-matrix interactions and assembling the extracellular matrix. The coiled-coil domain enables matrilin-3 to form both homo- and hetero-oligomers, primarily with matrilin-1, which is critical for its function in the ECM.

Function

The primary function of matrilin-3 is to mediate the interactions between collagen fibrils and other matrix components, contributing to the structural organization and mechanical properties of cartilage. It plays a significant role in cartilage development and maintenance, and its expression is tightly regulated during chondrogenesis. Matrilin-3 also interacts with other ECM proteins such as aggrecan, facilitating the formation of a resilient and elastic cartilage matrix.

Clinical Significance

Mutations in the MATN3 gene have been associated with several skeletal disorders, including multiple epiphyseal dysplasia (MED) and osteoarthritis (OA). MED is a genetically heterogeneous group of diseases characterized by abnormal development of the epiphyses and early-onset osteoarthritis. The mutations affecting matrilin-3 often lead to the misfolding of the protein, resulting in its retention in the endoplasmic reticulum and subsequent reduction in ECM deposition. This disruption in ECM assembly contributes to the pathogenesis of MED and OA by compromising the structural integrity and function of cartilage.

Research Directions

Current research on matrilin-3 focuses on understanding its precise role in cartilage biology and pathology, including its interactions with other ECM components and its regulation during cartilage development and disease. Insights into the molecular mechanisms underlying matrilin-3-related skeletal disorders may lead to the development of targeted therapies for conditions like MED and OA.

See Also

• Extracellular matrix
• Cartilage
• Multiple epiphyseal dysplasia
• Osteoarthritis