Bet Bromodomains’ Functions in Bone-Related Pathologies

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

Acknowledgments

The authors thank www.servier.fr for the free-access clipart, used in the figures.

Financial & competing interests disclosure

Thanks for the financial support of Fondation ARC, La Ligue Contre le Cancer, SFCE, ANR, Région Pays de la loire. The authors thank Cancéropôle Grand Ouest to support the Niches and Epigenetics of Tumors network, http://www.canceropole-grandouest.com. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Writing assistance was utilized from the American Manuscript editors.

Additional information

Funding

Thanks for the financial support of Fondation ARC, La Ligue Contre le Cancer, SFCE, ANR, Région Pays de la loire. The authors thank Cancéropôle Grand Ouest to support the Niches and Epigenetics of Tumors network, http://www.canceropole-grandouest.com. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. Writing assistance was utilized from the American Manuscript editors.