How Do Skeletal Tissues Keep Time? Circadian Rhythms in Cartilage and Bone

Abstract

The genetic decoding of the circadian clockwork has been a remarkable achievement in revealing the intricate molecular feedback loops that generate 24-hour rhythms. The discovery of cell-intrinsic circadian clocks in peripheral tissues has fueled further interest in investigating their tissue specific roles under both homeostatic and pathophysiological conditions throughout life. The skeletal system in mammals not only provides protection to internal organs and allows movement, but also generates blood cells and serves important endocrine functions, such as the regulation of mineral homeostasis. Importantly, the skeletal system seems to be particularly sensitive to the effects of ageing, as shown by the high prevalence of osteoarthritis (characterised by articular cartilage degeneration) and osteoporosis (loss of bone density), among others. Epidemiological studies have associated shift work, which frequently disrupts circadian rhythms, with low mineral density in bones, a greater risk of hip and wrist fractures and the development of osteoarthritis. In this chapter, we summarize the current understanding of the circadian timing mechanisms in cartilage and bone, with a particular focus on the evidence of circadian rhythms in physiology, their molecular underpinnings, tissue-specific targets, and their links to diseases. We also discuss the clinical relevance of utilising skeletal circadian rhythms to promote tissue health and slow down disease progression.