The distribution of Cartilage Oligomeric Matrix Protein (COMP) in tendon and its variation with tendon site, age and load

Abstract

A protein prominent in guanidine hydrochloride extracts of adult bovine and equine digital flexor tendons was confirmed to be Cartilage Oligomeric Matrix Protein (COMP) by non-reducing and reducing SDS-PAGE, reaction with rabbit anti-COMP polyclonal antiserum on Western blots, trypsin digestion followed by HPLC on a C2/C18 column, and identification of COMP mRNA from tendon on Northern blots. Immunohistochemistry and Western blots of extracts showed COMP to be present in all regions of digital flexor tendons. Equine tendon COMP was purified by ion exchange chromatography and gel filtration and used in a heterologous inhibition ELISA to quantify COMP in equine digital flexor tendons at different ages, and in other tendons and ligaments. Mean COMP levels in digital flexor tendon were approximately 2-5mg/g wet weight, but they showed a large variation. Levels were low in neonatal tendon but rose rapidly during growth, with the metacarpal (tensional) superficial digital flexor tendon having the highest levels (approximately 10mg/g wet weight). Levels subsequently declined in this region, while in areas which experience a variable amount of compression, levels increased less but then remained constant. Extensor tendons and collateral ligaments, which experience less loading in vivo, had levels similar to those in neonatal tendon. COMP was identified in scarred skin and granulation tissue but not in normal skin, chronic fibrosis, or a fibrosarcomatous skin growth. A unilateral non-weight-bearing growing animal contained three to six times more COMP in the weight-bearing digital flexor tendons compared to the paralyzed limb, while the extensor tendons had similar amounts in both limbs. With the recent discovery of a COMP gene mutation causing pseudoachondroplasia (Hecht et al., 1995), in which lax tendons and ligaments are a feature, the present data suggest that COMP is synthesized in response to, and is necessary for tendon to resist, load.