BMP and Beyond: A 25-Year Historical Review of Translational Spine Research at Emory University.

A high rate of symptomatic spinal pseudoarthrosis and a wide range of complications associated with the use of iliac crest bone graft (the gold standard) have prompted the spine surgery community to seek alternative options to promote spinal fusion. Emory University has been one of the global leaders in this endeavor. This invited review covers the last 25 years of Emory's contributions to translational spine research, focusing specifically on our work with bone morphogenetic proteins (BMP) and the BMP signaling pathway. As a result of this work, recombinant human BMP-2 is the only Food and Drug Administration approved biologic bone graft substitute. It has been shown to significantly increase spinal fusion rates across the spinal column because of its potent ability to stimulate local bone formation through the recruitment of mesenchymal stem cells. This review covers our development of animal models of spinal fusion, our body of work regarding the translation of BMP from the benchtop to the clinic, the discovery of LMP-1 and strategies to enhance cellular responsiveness to BMPs, and the design of various small molecule drugs that can enhance local bone formation.