Bone Regeneration

Rex Haydon, M.D., Ph.D., Assistant Professor of Surgery (Orthopaedic Surgery and Rehabilitation Medicine), joined the faculty in 2004 and is developing a clinical program in orthopaedic oncology that will be supported by his research in bone biology.

His interests stemmed originally from his training in physical anthropology and archeology, including excavation and analysis of mummified human remains recovered from two Pre-Inca mortuary sites in southern Peru. His doctoral work was conducted in the Howard Hughes Institute under the direction of Dr. Graeme Bell.

More recently he has explored the use of PPARg agonists, such as Troglitazone and Ciglitazone, as new systemic treatments for osteosarcoma. This research is currently being used to create clinical trials using PPARg agonists in patients with osteosarcoma.

Of broader interest to orthopaedics as a field, he is interested in identifying and exploring new approaches to bone regeneration that will improve upon current methods. Such improvements will almost certainly lead to highly innovative, and effective, clinical treatments for a broad range of orthopaedic disorders. His NIH Clinical Scientist Development Award (K08) has received an excellent score and is in the final stages of administrative review. This proposal evolved from his pilot study which helped to show that BMP6 induces osteoblastic differentiation more rapidly than any other BMP, and is among the three most potent BMPs.

The objective is to determine if Id1, Id2 and Id3 proteins play an important role in BMP6-induced bone formation. BMPs belong to the TGF-beta superfamily and are critical in skeletal development. Based on a comprehensive analysis of the in vitro and in vivo osteogenic activity of 14 BMPs, he and his colleagues have found that BMP6 is one of the most potent osteogenic BMPs. The Id proteins are among the most significantly up-regulated genes by osteogeneic BMPs and function as a dominant-negative regulator of basoic HLH (bHLH) transcription factors. While the dual functions of Id proteins (i.e., inhibiting differentiation and stimulating proliferation) are implicated in many developmental processes (e.g., myogenesis and bone morphogenesis), the actual role of Id proteins in BMP-induced osteogenesis remains obscure. This next step in his research will study the hypothesis that these genes are important early and direct targets of osteogenic BMP signaling. Improving our understanding of its signaling pathways and downstream targets, as well as its in vivo activity will help to guide our efforts to translate BMP-related research into novel clinical treatments.

The BMP signaling pathway. Mature BMP proteins form heterodimers that bind to the BMP receptors and activate their kinase activity, leading to the phosphorylation of Smads. Activated Smads are translocated to the nucleus and regulate the expression of target genes involved in cell proliferation and differentiation.

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Rex Haydon, MD, PhD

Haydon Group Links

Bone Regeneration