Rhythms in Remodeling: Posttranslational Regulation of Bone by the Circadian Clock.

Abstract

The circadian clock is a fundamental timekeeping system that regulates rhythmic biological processes in response to environmental light-dark cycles. In mammals, core clock genes (CLOCK, BMAL1, PER, and CRY) orchestrate these rhythms through transcriptional-translational feedback loops, influencing various physiological functions, including bone remodeling. Bone homeostasis relies on the coordinated activities of osteoblasts, osteoclasts, and osteocytes, with increasing evidence highlighting the role of circadian regulation in maintaining skeletal integrity. Disruptions in circadian rhythms are linked to bone disorders such as osteoporosis. Posttranslational modifications (PTMs), including phosphorylation, acetylation, and ubiquitination, serve as crucial regulators of both circadian mechanisms and bone metabolism. However, the specific role of PTMs in integrating circadian timing with bone remodeling remains underexplored. This review examines the intersection of circadian regulation and PTMs in bone biology, elucidating their impact on bone cell function and homeostasis. Understanding these interactions may uncover novel therapeutic targets for skeletal diseases associated with circadian disruptions.