The role of bone morphogenetic proteins in articular cartilage development, homeostasis and repair

Abstract

Bone morphogenetic proteins (BMPs) are members of the TGF-beta superfamily of secreted ligands. BMPs regulate a diverse range of developmental processes during embryogenesis and postnatal development, and control the differentiation of several musculoskeletal tissues including bone, cartilage, tendon and ligaments. The ability of BMPs to modulate the phenotype of cells in these tissue lineages suggests that these factors could be valuable for musculoskeletal tissue regeneration. In fact, BMPs-2 and -7 are already in clinical use for bone regeneration. This review addresses the signaling mechanisms by which BMPs regulate cellular processes, the role of BMPs in articular cartilage development and joint formation, and the data that supports the use of BMPs for in vitro phenotypic support of articular chondrocyte cultures, chondrogenic differentiation of mesenchymal stem cells (MSCs) and articular cartilage repair. Given the documented importance of BMP activity for normal joint formation, articular cartilage development and maintenance, the chondrogenic activity of BMPs when applied to MSC cultures and the encouraging outcomes of several in vivo cartilage repair studies, BMP therapies hold considerable promise for effective cartilage repair and/or regeneration. Future advances in the control of BMP elution from biocompatible matrices and prolonged, dose-controlled BMP expression by genetically engineered cells should substantially improve cartilage repair strategies using BMPs and similar chondro-protective proteins.