Insights into the Role of Circadian Rhythms in Bone Metabolism: A Promising Intervention Target?

Song, Chao; Wang, Jia; Kim, Brett; Lu, Chanyi; Zhang, Zheng; Liu, Huiyong; Kang, Huifang; Sun, Yunlong; Guan, Hanfeng; Fang, Zhong; Li, Feng

doi:10.1155/2018/9156478

Cited by 48 publications

(53 citation statements)

References 138 publications

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“…The association between sleep quality and bone outcomes has been previously explained as an effect of sleep deprivation on circadian rhythms and thus the consequent changes that occur in bone metabolism [27]. Disruptions in the circadian clock have indeed been linked to abnormal bone metabolism and osteoporosis [28]. In our study, bone outcomes changed according to biological sex, and this can be linked to the fact that sleep quantity and quality varies with biological sex [3].…”

Section: Discussionsupporting

confidence: 52%

Self-reported Sleep Quality and Bone Outcomes in Older Adults: Findings from the Hertfordshire Cohort Study

et al. 2020

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Sleep duration may be associated with risk of osteoporosis, with suggestions that too little or indeed too much sleep may be detrimental to bone health. In this study, we considered whether perceived sleep quality is also associated with bone health in older adults. We explored this association in a cohort of 443 older community-dwelling UK adults. Sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI); poor sleep quality was defined as > 5 on this score system. Bone density, shape and microarchitecture were assessed using dual energy X-ray absorptiometry (DXA), peripheral quantitative computed tomography (pQCT) and high-resolution pQCT (HRpQCT). Thirty-seven percent of men and 43% of women had a PSQI score greater than 5, indicative of poor perceived sleep. We found that quality of sleep was associated with altered bone microarchitecture. In men, poor sleep quality was associated with lower radial trabecular (4% slice, p < 0.04) and cortical (66% slice, p = 0.02) bone mineral density, as well as decreased tibial cortical density (p < 0.02) and increased porosity (p < 0.04), but increased size of the tibia (p < 0.04). In women, poor perceived sleep quality was associated with thinner (p < 0.03) and less dense (p < 0.04) cortices of the radius, but greater tibial trabecular number (p < 0.02) and lower separation (p < 0.04). Relationships with DXA parameters were non-significant after adjustment for confounders. Taking sleep medications was associated with decreased tibial size (38% and 66% slices) and strength in women (all p < 0.05), but not in men. Perceived sleep quality was associated with altered bone density and microarchitecture in older adults, and these differences varied according to biological sex and site. Further work is indicated to investigate possible mechanisms underlying these observations.

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Section: Discussionsupporting

confidence: 52%

Self-reported Sleep Quality and Bone Outcomes in Older Adults: Findings from the Hertfordshire Cohort Study

et al. 2020

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“…It is a sensitive point in the network because it is the only gene in a mouse model where single gene knockout causes arrhythmias at the molecular and behavioral levels (Bunger et al, 2000). BMAL1 has been shown to be important in bone metabolism because the bone mass of BMAL1 KO mice is lower than that of wild-type mice (Song et al, 2018). Recently, researchers have discovered the role of circadian rhythm in the musculoskeletal system (Song et al, 2018).…”

Section: Introductionmentioning

confidence: 99%

“…BMAL1 has been shown to be important in bone metabolism because the bone mass of BMAL1 KO mice is lower than that of wild-type mice (Song et al, 2018). Recently, researchers have discovered the role of circadian rhythm in the musculoskeletal system (Song et al, 2018). Recent studies have shown that chronic circadian rhythm disturbance interference is closely related to the development of osteoarthritis-like lesions of the knee joint in mouse, thus revealing circadian rhythm disturbance as a new risk factor for OA (Ranjan et al, 2015).…”

Section: Introductionmentioning

confidence: 99%

Circadian Rhythm Protein Bmal1 Modulates Cartilage Gene Expression in Temporomandibular Joint Osteoarthritis via the MAPK/ERK Pathway

Chen

Zhao

et al. 2020

Front. Pharmacol.

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The purpose of this study was to elucidate the role of the circadian gene Bmal1 in human cartilage and its crosstalk with the MAPK/ERK signaling pathway in temporomandibular joint osteoarthritis (TMJ-OA). We verified the periodical variation of the circadian gene Bmal1 and then established a modified multiple platform method (MMPM) to induce circadian rhythm disturbance leading to TMJ-OA. IL-6, pERK , and Bmal1 mRNA and protein expression levels were assessed by real-time RT-PCR and immunohistochemistry. Chondrocytes were treated with an ERK inhibitor (U0126), siRNA and plasmid targeting Bmal1 under IL-6 simulation; then, the cells were subjected to Western blotting to analyze the relationship between Bmal1 and the MAPK/ERK pathway. We found that sleep rhythm disturbance can downregulate the circadian gene BMAL-1 and improve phosphorylated ERK (p-ERK) and IL-6 levels. Furthermore, Bmal1 siRNA transfection was sufficient to improve the pERK level and aggravate OA-like gene expression changes under IL-6 stimulation. Bmal1 overexpression relieved the alterations induced by IL-6, which was consistent with the effect of U0126 (an ERK inhibitor). However, we also found that BMAL1 upregulation can decrease ERK phosphorylation, whereas ERK downregulation did not change BMAL1 expression. Collectively, this study provides new insight into the regulatory mechanism that links chondrocyte BMAL1 to cartilage maintenance and repair in TMJ-OA via the MAPK/ERK pathway and suggests that circadian rhythm disruption is a risk factor for TMJ-OA.

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“…Circadian clocks regulate various biochemical, cellular, and physiological processes with a periodicity of approximately 24 hours in order to maximize an organism's physiological efficiency . Studies have reported molecular links between circadian clocks and bone metabolism in mammals, including humans . For example, in humans, levels of the C‐terminal cross‐linked telopeptide of type I collagen (a bone resorption marker) and fibroblast growth factor 23 (a regulator of mineral metabolism) display a circadian rhythm .…”

Section: Discussionmentioning

confidence: 99%

Melatonin is a potential drug for the prevention of bone loss during space flight

Ikegame

Hattori

Tabata

et al. 2019

Journal of Pineal Research

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Astronauts experience osteoporosis‐like loss of bone mass because of microgravity conditions during space flight. To prevent bone loss, they need a riskless and antiresorptive drug. Melatonin is reported to suppress osteoclast function. However, no studies have examined the effects of melatonin on bone metabolism under microgravity conditions. We used goldfish scales as a bone model of coexisting osteoclasts and osteoblasts and demonstrated that mRNA expression level of acetylserotonin O‐methyltransferase, an enzyme essential for melatonin synthesis, decreased significantly under microgravity. During space flight, microgravity stimulated osteoclastic activity and significantly increased gene expression for osteoclast differentiation and activation. Melatonin treatment significantly stimulated Calcitonin (an osteoclast‐inhibiting hormone) mRNA expression and decreased the mRNA expression of receptor activator of nuclear factor κB ligand (a promoter of osteoclastogenesis), which coincided with suppressed gene expression levels for osteoclast functions. This is the first study to report the inhibitory effect of melatonin on osteoclastic activation by microgravity. We also observed a novel action pathway of melatonin on osteoclasts via an increase in CALCITONIN secretion. Melatonin could be the source of a potential novel drug to prevent bone loss during space flight.

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Insights into the Role of Circadian Rhythms in Bone Metabolism: A Promising Intervention Target?

Cited by 48 publications

References 138 publications

Self-reported Sleep Quality and Bone Outcomes in Older Adults: Findings from the Hertfordshire Cohort Study

Self-reported Sleep Quality and Bone Outcomes in Older Adults: Findings from the Hertfordshire Cohort Study

Circadian Rhythm Protein Bmal1 Modulates Cartilage Gene Expression in Temporomandibular Joint Osteoarthritis via the MAPK/ERK Pathway

Melatonin is a potential drug for the prevention of bone loss during space flight

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