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Epigenomics. 2020 Jan;12(2):127-144. doi: 10.2217/epi-2019-0172. Epub 2019 Dec 18.

BET bromodomains' functions in bone-related pathologies.

Author information

1
Nantes Université, INSERM, Bone sarcomas & remodeling of calcified tissues, UMR 1238, F-44000 Nantes, France.
2
'Niches & Epigenetics of Tumors' Network from Cancéropôle Grand Ouest.

Abstract

Throughout life, bones are subjected to the so-called 'bone-remodeling' process, which is a balanced mechanism between the apposition and the resorption of bone. This remodeling process depends on the activities of bone-specialized cells, namely the osteoblasts and the osteoclasts. Any deregulation in this process results in bone-related pathologies, classified as either metabolic nonmalignant diseases (such as osteoporosis) or malignant primary bone sarcomas. As these pathologies are not characterized by common targetable genetic alterations, epigenetic strategies could be relevant and promising options. Recently, targeting epigenetic regulators such as the bromodomains and extraterminal domains (BET) readers have achieved success in numerous other pathologies, including cancers. In this review, we highlight the current state of the art in terms of the diverse implications of BET bromodomain proteins in the bone's biology and its defects. Consequently, their role in bone-related pathologies will also be developed, especially in the context of the primary bone sarcomas.

KEYWORDS:

BET bromodomains; BRD4; Ewing sarcoma; I-BET; JQ1; bone; chondrosarcoma; epigenetic; osteoporosis; osteosarcoma

PMID:
31849242
DOI:
10.2217/epi-2019-0172

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