About Weirong Xing, PhD
My research interests are focused on the regulation of bone formation and bone resorption by ephrin B1 and leucine rich repeat kinase 1 (LRRK1) mediated signaling pathways. We have demonstrated that lack of ephrin B1 expression in osteoblasts resulted calvarial defects as well as reduced bone size and bone mineral density in mice. Conditional knockout of ephrin B1 in osteoclasts increased osteoclasts increased osteoclast differentiation and bone resorption in mice. Transgenic overexpression of ephrin B1 in bone cells increased bone formation.
We are currently investigating the role of novel bone resorptive regulator, LRRK1 in bone resorption in mice and humans. We have demonstrated that knockout of Lrrk1 gene in mice resulted in osteopetrosis phenotype that is much more severe than Sost or c-Src knockout mice. Precursors derived from Lrrk1 knockout mice differentiate into mature osteoclasts, but fail to resorb bone due to dysfunction of osteoclasts. Patients with mutations in the Lrrk1 gene exhibit a phenotype of osteosclerotic metaphyseal dysplasia characterized by severe osteosclerosis confined to the metaphysis of the long and short tubular bones due to osteoclast dysfunction. These observations make LRRK1 an ideal drug target for treatment of high bone turnover. Our ongoing studies will elucidate the molecular mechanisms of LRRK1 action in regulating osteoclast activity, and develop small molecular weight LRRK1 inhibitors that can be used for treatment and prevention of osteoporosis and osteoporotic fractures.