Cartilage oligomeric matrix protein is involved in human limb development and in the pathogenesis of osteoarthritis

Cartilage oligomeric protein (COMP) is a protein of the extracellular matrix and can be found in human articular cartilage [1], meniscus [2], and cruciate ligament and tendon [3]. Lower concentrations of COMP can also be detected in hyaline cartilage of the human rib and trachea [4]. It has also been extracted from animal skeletal tissues, such as bovine tendon and mouse, rat, and porcine cartilage [5]. COMP is an anionic, approximately 550-kDa disulfide-linked pentameric glycoprotein and, as a member of the thrombospondin gene family, is also called thrombospondin 5 [6]. Epidermal growth factor-like and calcium-binding repeats are located in the central region of the protein [7]. The function of COMP is still not completely understood, but it binds to chondrocytes in vitro [8]. COMP has been shown to bind to matrilins [9] and collagen types I, II, and IX [10,11]. In contrast, COMP has no affinity to the other members of the thrombospondin family [12]. The DNA-binding protein SP1 regulates COMP expression [13] and also mechanical compression of chondrocytes [14]. COMP expression has been shown to be inhibited by leukemia/lymphoma-related factor (LRF) [15]. The human COMP gene is located on chromosome 19 [7]. Mutations of this gene can cause pseudoachondroplasia and multiple epiphysial dysplasia [16-18]. Furthermore, COMP has been shown to be upregulated after traumatic knee injury [19] and has been implicated in the pathogenesis of rheumatoid arthritis [20] and osteoarthritis (OA) [12,21]. During mouse development, COMP staining has been described around maturing articular chondrocytes [22], and during rat development it has been associated mainly with the growth plate [23]. Fang and colleagues [24] detected COMP as early as day 10 in murine development in the condensing mesenchyme, and later it was found in the growth plate and superficially in the developing joint cartilage. At the time of birth, COMP has been detected in the perichondrium, the periosteum, and the