Alexandria Smith
University of Texas Medical Branch
Many processes in the human body, including activity and gene expression, oscillate over the course of a 24-hour cycle known as the circadian rhythm. This rhythm plays a critical role in maintaining homeostasis, and disruption is implicated in the development of several musculoskeletal diseases. This literature review explores the molecular mechanisms of the circadian rhythm, how it is disrupted, and the impact of disruption on the musculoskeletal system. Throughout the body, the majority of cells have an intrinsic rhythm maintained through the rhythmic oscillation of four clock proteins: BMAL1, CLOCK, Per and Cry. BMAL1 and Clock are synthesized and form a heterodimer that translocates to the nucleus to activate the transcription of many genes, including Per and Cry. Once translated, Per and Cry form a heterodimer that translocates to the nucleus and inhibits the activity of the BMAL1:CLOCK heterodimer. Maintenance of synchronization across cells is achieved through signals from the suprachiasmatic nucleus of the brain. Exposure to light at night, increased evening activity, and various other mechanisms can disrupt the circadian rhythm. Disruption is linked to muscle atrophy, intervertebral disc degeneration, low bone mass, and osteoarthritis. Emerging areas of research include methods to prevent rhythm disruption, timing of drug administration to maximize efficacy, and pharmacologic treatments targeting clock proteins. Understanding the role of circadian rhythms in homeostasis has shed light on the pathogenesis of several chronic degenerative musculoskeletal diseases and opened the door to development of innovative management options.
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