Differential response of cartilage oligomeric matrix protein (COMP) to morphogens of bone morphogenetic protein/transforming growth factor-β family in the surface, middle and deep zones of articular cartilage

Abstract

Cartilage oligomeric matrix protein (COMP) is a prominent non-collagenous component of the extracellular matrix (ECM) in articular cartilage. The regulation of COMP synthesis and secretion is critical for the understanding of cartilage homeostasis in health and disease. We therefore investigated the role of bone morphogenetic protein/transforming growth factor-β (BMP/TGFβ) superfamily members on COMP. Articular chondrocytes were isolated from three distinct zones (surface, middle and deep) and cultured as monolayers in serum-free chemically defined medium. Protein levels of COMP were determined in the medium by enzyme-linked immunosorbent assay. The mRNA expression was determined by quantitative real-time reverse-transcription polymerase chain reaction (RT-PCR). TGFβ1 significantly stimulated the expression of COMP at the mRNA and protein levels in the superficial zone in a time-dependent manner. An unexpected discovery was that surface chondrocytes were more responsive to TGFβ isoforms than those in the deep layer. However, BMP-7 and growth differentiation factor-5 (GDF-5) also upregulate COMP expression; the effects were not as potent as those of TGFβ1. Activins A, B and AB demonstrated no effects on COMP in any of the zones. In conclusion, COMP synthesis is differentially regulated by TGFβ1 in the surface and middle zones of bovine articular cartilage.