Rheumatology: Current Research
Open Access

Inhibition of osteoclastogenesis and inflammatory bone resorption by targeting BET proteins and epigenetic regulation

5^th International Conference of Orthopedic Surgeons and Rheumatology

June 16-17, 2016 Alicante, Spain

Kyung-Hyun Park-Min

Hospital for Special Surgery, USA

Posters & Accepted Abstracts: Rheumatology (Sunnyvale)

Abstract :

Epigenetics is becoming increasingly appreciated as a new area of research that may provide insights into the pathogenesis of inflammatory autoimmune diseases such as rheumatoid arthritis (RA). Epigenetics refers to the control of gene expression by chromatin regulators, modifications of chromatin components such as histones, DNA methylation, or non-coding RNAs. Recent drugs targeting epigenetic processes have shown great promise for the treatment of cancers and inflammatory conditions. Receptor activator of nuclear kappa B ligand (RANKL) is a key inducer of osteoclastogenesis and emerging evidence suggests that RANKLinduced histone modifications are important for osteoclastogenesis. However, these epigenetic mechanisms in osteoclasts are not well understood and have not been therapeutically targeted. Thus, we have investigated the epigenetic regulation of osteoclast differentiation. We find that the small molecule inhibitor, I-BET151 that targets bromo and extra-terminal (BET) proteins that �read� chromatin states by binding to acetylated histones strongly suppresses osteoclastogenesis. Interestingly, I-BET151 attenuates inflammatory arthritis by diminishing both inflammation and bone resorption and protects mice from oestrogen deficiency induced osteoporosis. Through transcriptome analysis, we reveal an important role of a MYC/NFAT axis in osteoclasts that is elevated in RA osteoclast precursors. I-BET151 suppresses osteoclastogenesis by, in part, inhibiting a MYC/NFATc1 axis. These findings implicate the importance of MYC and BET proteins in osteoclast differentiation and demonstrate that targeting an epigenetic molecule in osteoclasts can be effective in suppressing the pathological bone resorption. Taken together, our study opens up a new line of investigation in the understanding and therapeutic targeting of pathological bone resorption..

Biography :

Email: parkminK@HSS.EDU