Division of Bone Research

Bone Research Laboratory

Director: Chi Zhang, M.D., Ph.D.

Osterix (Osx) is a bone-specific transcription factor required for osteoblast commitment and bone formation. Bone research laboratory is interested in studying molecular mechanisms of Osx effect on bone formation both in vitro and in vivo using molecular and cell biological and genetic approaches. We also develop clinical and translational research to gain insight into the pathogenesis and cure of orthopedic diseases.

Research Projects:

1. Molecular mechanisms of Osx effect on bone formation and bone remodeling

Bone formation is a complex developmental process involving the differentiation of mesenchymal stem cells to osteoblasts. The osteocyte is a terminally differentiated cell type of the osteoblast lineage. Osteoblast differentiation occurs through a multistep molecular pathway regulated by different transcription factors and signaling proteins, including Ihh, Runx2, Osx, and Wnt signaling. One new discovery of our studies is that Osx inhibits Wnt pathway signaling, a possible mechanism for Osx to inhibit osteoblast proliferation. The purpose of current research project is to identify and characterize the downstream genes of Osx and to further explore the molecular mechanisms of Osx effect on bone formation and bone remodeling. This project is supported by research grant from Arthritis Foundation.

2. Effect of hypoxia-inducible factor-1 on chondrocyte activity and angiogenesis in femoral head osteonecrosis.

Legg-Calvé-Perthes disease is a juvenile form of ischemic osteonecrosis of the femoral head that can produce femoral head deformity and premature osteoarthritis.  It remains one of the most challenging conditions to treat due to our lack of understanding of the biology of the disease. Femoral head osteonecrosis occurs due to disruption of blood supply which produces hypoxic injury to the femoral head cartilage and bone. Hypoxia-inducible factor-1 (HIF-1) is a master regulator of cellular response to hypoxia. Our preliminary studies suggest that hypoxia activates chondrocyte activity. This project is to examine effect of HIF-1 on chondrocyte activity and angiogenesis. We cooperate with Dr. Harry Kim in this project.

3. Identification of potential candidate genes associated with high degree thumb polydactyly

Polydactyly is the most frequent human congenital hand deformity, and it is inherited as an autosomal dominant trait. In our hospital, there are some patients with this disease in two different families. These thumbs have higher levels of polydactyly that there are elements of at least three thumbs on one hand. We are interested in using molecular genetic approaches to identify potential candidate genes associated with high degree thumb polydactyly. We cooperate with Dr. Marybeth Ezaki in this project.