Use of bone morphogenetic proteins in mesenchymal stem cell stimulation of cartilage and bone repair

Abstract

The extracellular matrix-associated bone morphogenetic proteins (BMPs) govern a plethora of biological processes. The BMPs are members of the transforming growth factor-β protein superfamily, and they actively participate to kidney development, digit and limb formation, angiogenesis, tissue fibrosis and tumor development. Since their discovery, they have attracted attention for their fascinating perspectives in the regenerative medicine and tissue engineering fields. BMPs have been employed in many preclinical and clinical studies exploring their chondrogenic or osteoinductive potential in several animal model defects and in human diseases. During years of research in particular two BMPs, BMP2 and BMP7 have gained the podium for their use in the treatment of various cartilage and bone defects. In particular they have been recently approved for employment in non-union fractures as adjunct therapies. On the other hand, thanks to their potentialities in biomedical applications, there is a growing interest in studying the biology of mesenchymal stem cell (MSC), the rules underneath their differentiation abilities, and to test their true abilities in tissue engineering. In fact, the specific differentiation of MSCs into targeted cell-type lineages for transplantation is a primary goal of the regenerative medicine. This review provides an overview on the current knowledge of BMP roles and signaling in MSC biology and differentiation capacities. In particular the article focuses on the potential clinical use of BMPs and MSCs concomitantly, in cartilage and bone tissue repair.

Keywords: Mesenchymal stem cells, Cartilage, Bone repair, Bone morphogenetic protein

Core tip: Since their first identification, bone morphogenetic proteins (BMPs) have attracted the attention for their potential therapeutic use in tissue engineering and biomedical regenerative therapies. In particular, BMP2 and BMP7 have been successfully used in the treatment of a number of cartilage and bone defects, although these strategies present a certain number of concerning side effects. Also in the field of mesenchymal stem cell (MSC) biology there is a continually growing interest, especially in the regulation of their differentiation, and in demonstrating their utility in tissue engineering. The review focuses on the current knowledge of BMP physiological roles in MSC biology and differentiation capacities. In particular it highlights the potentialities of the concomitant clinical use of BMPs and MSCs in cartilage and bone tissue repair.