The inhibition of BET leads to a suppression of osteoclastogenesis

 

Osteoclastogenesis is a process that generating osteroclasts, which are able to resorb bone tissue, for the maintenance of bone homeostasis. However, the mechanism of the regulation of osteoclast differentiation has not been fully understood. Park-Min et al. found the inhibitor of bromo and extra-terminal (BET), I-BET151, can strongly reduce osteocelstogenesis. The article was published on Nature Communication.

 

One of the key factors that required in osteoclastogenesis is RANK ligand (RANKL). RANKL mediates myeloid lineage cells differentiate into osteoclasts, by activate multiple pathways to induce a transcription factor NFATc1, which is critical for osteoclastogenesis. In addition, it has been reported that RANKL can change osteoclast precursors' chromatin state during osteoclastogenesis. Researchers used TNF-induced inflammatory osteolysis, inflammatory arthritis and post-ovariectomy models, found I-BET151 can read chromatin states and inhibit the expression of NFATc1 by regulating the upstream signaling MYC. Therefore, I-BET151 can suppress osteoclast differentiation and osteoclastogenesis by targeting MYC-NFAT pathway, and it may become a promising clinical application in treatment of pathological bone resorption which is caused by inflammatory and oestrogen dificiency.

 

Reference:
Nat Commun. 2014 Nov 13;5:5418.

Related Products

Cat.No.	Product Name	Information
S7189	Molibresib (I-BET-762)	Molibresib (I-BET-762, GSK525762, GSK525762A) is an inhibitor for BET proteins with IC50 of ~35 nM in a cell-free assay, suppresses the production of proinflammatory proteins by macrophages and blocks acute inflammation, highly selective over other bromodomain-containing proteins.

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Epigenetic Reader Domain