Site Search:

The IU School of Medicine is a major center for skeletal research, and the on-going studies on normal and pathological bone biology have informed the development of therapeutics for osteoporosis and other diseases of bone.

Recent progress in treating all kinds of bone diseases has been due largely to our better understanding of how normal bone works. Embedded within and surrounding the cement-like bone is living cells and blood vessels that act to continuously turnover, or remodel, the mineralized skeleton. This remodeling insures the structural integrity of the bones and the proper amount of calcium and phosphorus in the blood.

There are bone-forming cells (osteoblasts) and bone-resorbing cells (osteoclasts). The actions of these cells are delicately balanced by numerous molecules released by the bone cells themselves and immune cells. These molecules are pro-inflammatory cytokines, growth factors, and hormones. These powerful agents direct not only the action of osteoblasts and osteoclasts but regulate their programmed death, an important part of maintaining healthy bone.

Many diseases of bone can be understood, in part, by defects in the remodeling process or the expression of molecules that regulate this process. Likewise, we are studying osteosarcoma, particularly its resistance to treatment, within this context. Treatment for osteosarcoma and other cancers can induce osteoporosis in patients, thus insights into one disease may inform our understanding of the other.

Architectural transcription factors (ATFs) or ATF-like proteins alter gene expression by bending or looping the DNA containing the target gene. High mobility group box 1 protein (HMGB1) is an ATF that also is secreted by immune cells as a potent immuno-modulatory factor and pro-inflammatory cytokine. Recent evidence indicates that the release of HMGB1 by various cancer cells plays a yet undefined role in tumorigenesis and metastasis. Also, recent evidence has determined that HMGB1 protects some osteosarcoma cells from cisplatin, which is a dominant drug used in chemotherapy.

A current objective is to elucidate the role of HMGB1 in normal bone physiology, osteosarcoma etiology, and osteosarcoma chemoresistance. Our principal resource for studying osteosarcoma is access to over 10 independent research laboratories engaged in the study of all aspects of bone biology.