期刊
FASEB JOURNAL
卷 34, 期 1, 页码 1052-1064出版社
FEDERATION AMER SOC EXP BIOL
DOI: 10.1096/fj.201901929R
关键词
bone mineralization; bone structure; bone turnover; circadian rhythm; clock genes
资金
- Leiden University Fund / Elise Mathilde Fund
- Board of Directors of Leiden University Medical Center
- Dutch Heart Foundation [2017T016]
- European Foundation for the Study of Diabetes [RS FS 2016_3]
- European Foundation for the Study of Diabetes [RS FS 2016_3] Funding Source: researchfish
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 rhythmicity has not yet been extensively studied in bone. Here, we investigated which genes are rhythmically expressed in bone, and whether circadian disruption by shifts in light-dark cycle affects bone turnover and structure in mice. Our results demonstrate diurnal expression patterns of clock genes (Rev-erb alpha, 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 light-dark 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 bone strength in the long term. Collectively, these results show that a physiological circadian rhythm is important to maintain bone health, which stresses the importance of further investigating the association between shift work and skeletal disorders.
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