Bone erosion and fragility fractures are associated with rheumatoid arthritis and postmenopausal osteoporosis, representing a major unmet clinical problem. In health, the balance between osteoblasts and osteoclasts is a dynamic process under tight regulation. In disease, regulation is uncontrolled resulting in overt bone loss. NF-κB is a master regulator of cellular function and is an essential element in the development and homeostasis of the skeletal system. As such, it is a critical controller of both osteoblast and osteoclast differentiation and function. Bcl-3 is an atypical IκB protein and via its selective interaction with homodimers of NF-κB is a critical negative regulator of cellular function. Work in our laboratory has now established that mice deficient in Bcl-3 have increased bone mass, and that in vitro culture of their osteoblast precursors results in enhanced differentiation and function. Here, we investigate the role Bcl-3 plays in osteoblast and osteoclast generation and function. Furthermore, in vivo studies will determine whether the loss of Bcl-3 can provide protection from bone loss in a murine model of postmenopausal osteoporosis. These studies will provide pre-clinical supporting data to validate Bcl-3 as a novel target for the treatment of osteoporosis and other diseases associated with bone pathology.
Disclosure: The authors declared no competing interests. This work was supported by the Wellcome Trust (099786/Z/12/A) and travel support was provided by the Biochemical Society (GTGNOV2014).