Role of histone modification in the occurrence and development of osteoporosis

Abstract

Osteoporosis is a systemic degenerative bone disease characterized by low bone mass and damage to bone microarchitecture, which increases bone fragility and susceptibility to fracture. The risk of osteoporosis increases with age; with the aging of the global population, osteoporosis is becoming more prevalent, adding to the societal healthcare burden. Histone modifications such as methylation, acetylation, ubiquitination, and ADP-ribosylation are closely related to the occurrence and development of osteoporosis. This article reviews recent studies on the role of histone modifications in osteoporosis. The existing evidence indicates that therapeutic targeting of these modifications to promote osteogenic differentiation and bone formation may be an effective treatment for this disease.

Keywords: differentiation; histone modification; osteoblast; osteoclast; osteoporosis.

Figure 1

Role of SIRT1/6/7 in bone remodeling. In BMSCs, SIRT1, SIRT6, and SIRT7 promote osteogenic differentiation by regulating transcription factors FoxO3, β-catenin, Runx2, Osx, and PPARγ. In pre-osteoblasts, SIRT6 not only regulates Runx2 and Osx transcription, but also inhibits DKK1 transcription, activates canonical Wnt signaling, and promotes osteogenic differentiation. In BMMs, SIRT1 inhibits osteoclast differentiation by regulating FoxO and TNF-α transcription, which results in ROS scavenging.