Distinct roles of bone morphogenetic proteins in osteogenic differentiation of mesenchymal stem cells

TLDR

Bone regeneration could transform treatment of bone disorders, and bone morphogenetic proteins (BMPs) regulate mesenchymal stem cell differentiation, yet a comprehensive comparison of BMP osteogenic activity had not been performed before this study. The study aims to identify osteogenic BMPs and explore synergistic combinations for effective bone regeneration. Using adenoviral delivery of 14 BMPs, BMP6 and BMP9 were found to have the strongest osteogenic activity, and several BMPs synergistically enhanced differentiation, revealing distinct molecular signatures that broaden our knowledge of BMP function. © 2007 Orthopaedic Research Society; published by Wiley Periodicals, Inc., J Orthop Res 25:665–677, 2007.

Abstract

Abstract Efficacious bone regeneration could revolutionize the clinical management of many bone and musculoskeletal disorders. Bone morphogenetic proteins (BMPs) can regulate the differentiation of mesenchymal stem cells into cartilage, bone, tendon/ligament, and fat lineages. Early data documented the osteogenic potential of rhBMP2 and rhBMP7/OP‐1. However, prior to this work that summarized several of our recent studies, no comprehensive analysis had been undertaken to characterize relative osteogenic activity of all BMPs. Using recombinant adenoviruses expressing 14 BMPs, we have demonstrated that, besides BMP2 and BMP7, BMP6 and BMP9 exhibit the highest osteogenic activity both in vitro and in vivo. We further demonstrated that several BMPs may exert synergistic effect on osteogenic differentiation, and that osteogenic BMPs produce a distinct set of molecular fingerprints during osteogenic differentiation. The reported work should expand our current understanding of BMP functions during osteogenic differentiation. It is conceivable that osteogenic BMPs (i.e., BMP2, 4, 6, 7, and 9) may be used to formulate synergistic pairs among themselves and/or with other less osteogenic BMPs for efficacious bone regeneration in clinical settings. © 2007 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 25:665–677, 2007