Distinct Roles of Bone Morphogenetic Proteins in Osteogenic Differentiation of Mesenchymal Stem Cells

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 andBMP9 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 BMPsproduceadistinct set ofmolecularfingerprintsduringosteogenic differentiation.The reported work should expand our current understanding of BMP functions during osteogenic differentiation. It is conceivable that osteogenicBMPs (i.e.,BMP2, 4, 6, 7, and9)maybeused to formulate synergistic pairs among themselves and/or with other less osteogenic BMPs for efficacious bone regeneratio