Circadian Clock Regulates Bone Resorption in Mice

The past decade, it has become evident that circadian rhythms within metabolically active tissues are very important for physical health. However, although shift work has also been associated with an increased risk of fractures, circadian rhythmicityhas not yet been extensively studied in bone. Here, we investigated which genes are rhythmically expressed in bone, and whether circadian disruption by shifts in lightdark cycle affects bone turnover and structure in mice. Our results demonstrate diurnal expression patterns of clock genes (Rev-erbα, Bmal1, Per1, Per2, Cry1, Clock), as well as genes involved in osteoclastogenesis, osteoclast proliferation and function (Rankl, Opg, Ctsk), and osteocyte function (c-Fos) in bone. Weekly alternating lightdark cycles disrupted rhythmic clock gene expression in bone and caused a reduction in plasma levels of procollagen type 1 amino-terminal propeptide (P1NP) and tartrate-resistant acidic phosphatase (TRAP), suggestive of a reduced bone turnover.These effects coincided with an altered trabecular bone structure and increased cortical mineralization after 15 weeks of light-dark cycles, which may negatively affect

No abstract

The circadian system in mammals is responsible for the temporal coordination of multiple physiological and behavioural processes that are necessary for homeostasis. In the skeleton, it has long been known that metabolic functions of chondrocytes, osteoblasts and osteoclasts exhibit intrinsic circadian rhythms. In addition, results from animal models reveal a close connection between the disruption of circadian rhythms and skeletal disorders such as rheumatoid arthritis, osteoarthritis and osteoporosis. In this review, we summarise the latest insights into the genetic and biochemical mechanisms linking cartilage and bone physiology to the circadian clock system. We also discuss how this knowledge can be utilised to improve human health.