HDAC7 KO osteoclasts show increased sensitivity to RANK-L cytokine

Abstract

Bone homeostasis is a balance between osteoclast-mediated bone resorption and osteoblast-mediated bone formation. Two cytokines, M-CSF and RANK-L are known to be necessary in osteoclast differentiation. Histone deacetylases (HDACs) are key regulators of gene expression, and recently have been shown to be important modulators in osteoclast differentiation. In previous research, HDAC7 has been shown to be a negative regulator of osteoclastogenesis. Osteoclasts from HDAC7 KO mice are increased in size and number. This study aims to test the hypothesis that osteoclasts from HDAC7 KO mice are hypersensitive to M-CSF and/or RANK-L. Results from my study demonstrate enhanced osteoclast differentiation in size and number of osteoclasts and resorption under varying M-CSF and RANK-L concentrations in HDAC7 KO compared to wild type osteoclasts. Mechanistically the hypersensitivity may be explained because HDAC7 KO osteoclasts had increased C-fms and RANK expression compared to wild type osteoclasts. Further research is necessary to determine if the hypersensitivity is due to increased gene expression by transcription factors MITF and PU.1.