ECTS Abstracts (2015) 1 P178

The Role of NF-Kb Regulator Bcl-3 in Osteoimmune Health and Disease

Hussain Jaffery1, James Doonan2, Moeed Akbar1, Ruaidhrí Carmody1 & Carl Goodyear1

1Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow, UK, 2Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow, UK.

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).

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