Bone morphogenetic proteins in the development and healing of synovial joints

Objectives: To review current knowledge of the role of bone morphogenetic proteins (BMPs) in joint formation and how this may be relevant to healing in adult joints. Method. Review of published literature using a search of the PubMed database (1966 to 2000) made available by the National Library of Medicine. Additional articles of historical interest were identified from the bibliographies of published literature. Results: BMPs and a related family, the growth and differentiation factors (GDFs), are stimulators of bone and cartilage formation in the developing skeleton. They, together with their antagonists, play key roles in the specification of the joint site and cavitation of synovial joints during embryonic development. Disruption of the GDF-5 gene in mice and humans is associated with abnormal joint formation. In situ hybridization studies have shown that BMPs are expressed during formation of synovial joints in the embryo. However, excessive BMP activity leads to obliteration of joints because of cartilage overgrowth. BMPs are being considered as therapeutic agents to stimulate healing of articular cartilage after damage. Evidence suggests that BMPs are present in adult joints and have roles in healing and maintenance. However, inflammatory cytokines and growth factors present in damaged joints modulate the actions of BMPs. Conclusions: BMPs, and in particular GDF-5, are involved in synovial joint formation. They may also have effects on the maintenance and healing of adult joints, but factors present after damage may alter their effectiveness. Relevance: Articular cartilage heals poorly after damage. BMPs may be useful therapeutically to stimulate healing of damaged articular cartilage. Increased knowledge of their role in joint formation will improve understanding of how to use them. Copyright (C) 2001 by W.B. Saunders Company.