BMP Signaling in Articular Cartilage Repair and Regeneration: Potential Therapeutic Opportunity for Osteoarthritis

Abstract

Eight years ago we reviewed the role of bone morphogenetic proteins (BMPs) in articular cartilage repair in the last edition of this series on BMPs. Since that time our understanding of the function of BMPs and especially BMP-7, also called osteogenic protein-1 (OP-1), in cartilage homeostasis and repair has significantly increased. The primary focus of this chapter is the potential therapeutic opportunity for BMPs in the treatment of osteoarthritis. The intervening data confirm that among BMPs, BMP-7 exhibits the most robust evidence supporting its use for cartilage repair and regeneration. In the current review, we continue to unravel more of the underlying mechanisms of the anabolic and anti-catabolic activities of BMPs to provide a better understanding of the interactions between BMPs and signaling pathways and highlight the increased role BMP-7 and other BMPs play in human cartilage homeostasis. In regard to in vivo activities, exciting new data have been published demonstrating that BMP-7, in multiple models of osteoarthritis, can delay or inhibit degradation of the articular cartilage. Most interesting is that for the first time, a clinical trial has been reported, and Phase I data evaluation of the effect of a single injection of BMP-7 into osteoarthritic knees demonstrated enough of a positive response to warrant a Phase II study. Together, recent studies continue to indicate a significant opportunity for BMPs and particularly BMP-7 as therapeutics for osteoarthritis.