Growth factors that drive aggrecan synthesis in healthy articular cartilage. Role for transforming growth factor-ß?

ABSTRACT

Introduction: Articular cartilage makes smooth movement possible and destruction of this tissue leads to loss of joint function. An important biomolecule that determines this function is the large aggregating proteoglycan of cartilage, aggrecan. Aggrecan has a relatively short half-life in cartilage and therefore continuous production of this molecule is essential. Methods: In this narrative review we discuss what is the role of growth factors in driving the synthesis of aggrecan in articular cartilage. A literature search has been done using the search items; cartilage, aggrecan, explant, Transforming Growth factor-ß (TGF-ß), Insulin-like Growth Factor (IGF), Bone Morphogenetic Protein (BMP) and the generic term "growth factors". Focus has been on studies using healthy cartilage and models of cartilage regeneration have been excluded. Results: In healthy adult articular cartilage IGF is the main factor that drives aggrecan synthesis and maintains adequate levels of production. BMP's and TGF-ß have a very limited role but appear to be more important during chondrogenesis and cartilage development. The major role of TGF-ß is not stimulation of aggrecan synthesis but maintenance of the differentiated articular cartilage chondrocyte phenotype. Conclusion: TGF-ß is a factor that is generally considered as an important factor in stimulating aggrecan synthesis in cartilage but its role in this might be very restrained in healthy, adult articular cartilage.