thrombospondin5

Thrombospondin-5, also known as cartilage oligomeric matrix protein (COMP), is a secreted extracellular matrix glycoprotein that belongs to the thrombospondin family. It is encoded by the COMP gene in humans and is primarily expressed in cartilage, with smaller amounts found in tendon, ligament, and other connective tissues.

COMP is a secreted, pentameric protein that assembles into a homopentameric complex in the extracellular matrix. It localizes to the cartilage matrix and contributes to the structural integrity of the tissue by interacting with various matrix components. COMP binds to collagen types II, IX, and XI, and interacts with other matrix proteins such as matrilins, helping to organize and stabilize the collagen network. It also influences cell-matrix interactions, potentially affecting chondrocyte behavior through surface receptors.

In development and adulthood, COMP is abundant in developing cartilage and growth plates, and remains a component of mature articular cartilage. It plays a role in maintaining cartilage structure and function, and its expression can be altered in joint diseases.

Genetically, COMP mutations cause autosomal dominant skeletal dysplasias, most notably pseudoachondroplasia and multiple epiphyseal dysplasia, which feature short stature, joint abnormalities, and early-onset degenerative changes. Biochemically, misfolded COMP due to mutations can accumulate in the endoplasmic reticulum of chondrocytes, contributing to cellular stress and disrupted matrix assembly.

Serum or synovial fluid levels of COMP rise with cartilage turnover and damage, making COMP useful as a biomarker in osteoarthritis and cartilage injury research. Ongoing studies investigate COMP’s role in cartilage biology and its potential as a therapeutic target for cartilage repair and regeneration.