Circadian clock genes as promising therapeutic targets for bone loss

Qu, Yi; Chen, Zhonghua; Wu, Junjie; Zhang, Zhenyu; Yuan, Zheng‐Dong; Guo, Dan‐Yang; Chen, Meng-Nan; Li, Xia; Yuan, Feng‐Lai

doi:10.1016/j.biopha.2022.114019

Cited by 8 publications

(5 citation statements)

References 106 publications

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“…Bone‐derived hormones also impact systemic energy metabolism, with FGF23 and OCN produced by osteocytes acting in a classical endocrine manner. Their expression levels are also under circadian control 57 . OCN regulates glucose metabolism by promoting pancreatic β‐cell proliferation and insulin secretion and can influence lipid metabolism by upregulating adiponectin.…”

Section: The Diurnal Rhythms In Bonementioning

confidence: 99%

“…Their expression levels are also under circadian control. 57 OCN regulates glucose metabolism by promoting pancreatic βcell proliferation and insulin secretion and can influence lipid metabolism by upregulating adiponectin. FGF23, through the FGFR/Klotho receptor complex, controls energy and mineral homeostasis through feedback loops with FGF23, vitamin D, and PTH.…”

Section: Mechanismsmentioning

confidence: 99%

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The specificities, influencing factors, and medical implications of bone circadian rhythms

Mei,

Wang,

Wang

et al. 2024

The FASEB Journal

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Physiological processes within the human body are regulated in approximately 24‐h cycles known as circadian rhythms, serving to adapt to environmental changes. Bone rhythms play pivotal roles in bone development, metabolism, mineralization, and remodeling processes. Bone rhythms exhibit cell specificity, and different cells in bone display various expressions of clock genes. Multiple environmental factors, including light, feeding, exercise, and temperature, affect bone diurnal rhythms through the sympathetic nervous system and various hormones. Disruptions in bone diurnal rhythms contribute to the onset of skeletal disorders such as osteoporosis, osteoarthritis and skeletal hypoplasia. Conversely, these bone diseases can be effectively treated when aimed at the circadian clock in bone cells, including the rhythmic expressions of clock genes and drug targets. In this review, we describe the unique circadian rhythms in physiological activities of various bone cells. Then we summarize the factors synchronizing the diurnal rhythms of bone with the underlying mechanisms. Based on the review, we aim to build an overall understanding of the diurnal rhythms in bone and summarize the new preventive and therapeutic strategies for bone disorders.

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Section: The Diurnal Rhythms In Bonementioning

confidence: 99%

Section: Mechanismsmentioning

confidence: 99%

The specificities, influencing factors, and medical implications of bone circadian rhythms

Mei,

Wang,

Wang

et al. 2024

The FASEB Journal

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“…Circadian regulation of physiological osteogenesis and pathological bone resorption in osteoarthritis, osteoporosis, and other diseases has been extensively studied [58][59][60]. However, the roles of Bmal1 in osteoclastogenesis remain unsettled, with contradictory studies reported by multiple groups.…”

Section: Circadian Regulation Of Osteoclastogenesismentioning

confidence: 99%

Circadian Regulation of Macrophages and Osteoclasts in Rheumatoid Arthritis

Kikyo

2023

IJMS

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Rheumatoid arthritis (RA) represents one of the best examples of circadian fluctuations in disease severity. Patients with RA experience stiffness, pain, and swelling in afflicted joints in the early morning, which tends to become milder toward the afternoon. This has been primarily explained by the higher blood levels of pro-inflammatory hormones and cytokines, such as melatonin, TNFα, IL-1, and IL-6, in the early morning than in the afternoon as well as insufficient levels of anti-inflammatory cortisol, which rises later in the morning. Clinical importance of the circadian regulation of RA symptoms has been demonstrated by the effectiveness of time-of-day-dependent delivery of therapeutic agents in chronotherapy. The primary inflammatory site in RA is the synovium, where increased macrophages, T cells, and synovial fibroblasts play central roles by secreting pro-inflammatory cytokines, chemokines, and enzymes to stimulate each other, additional immune cells, and osteoclasts, ultimately leading to cartilage and bone erosion. Among these central players, macrophages have been one of the prime targets for the study of the link between circadian rhythms and inflammatory activities. Gene knockout experiments of various core circadian regulators have established that disruption of any core circadian regulators results in hyper- or hypoactivation of inflammatory responses by macrophages when challenged by lipopolysaccharide and bacteria. Although these stimulations are not directly linked to RA etiology, these findings serve as a foundation for further study by providing proof of principle. On the other hand, circadian regulation of osteoclasts, downstream effectors of macrophages, remain under-explored. Nonetheless, circadian expression of the inducers of osteoclastogenesis, such as TNFα, IL-1, and IL-6, as well as the knockout phenotypes of circadian regulators in osteoclasts suggest the significance of the circadian control of osteoclast activity in the pathogenesis of RA. More detailed mechanistic understanding of the circadian regulation of macrophages and osteoclasts in the afflicted joints could add novel local therapeutic options for RA.

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“…These findings suggest that disruption of core-clock genes and CCGs can have a significant impact on behavioural and neural outputs of the CNS. (McCarthy et al, 2007) and bone metabolism (Qin et al, 2023).…”

Section: Neuronal Plasticity and Circadian Regulationmentioning

confidence: 99%

“…In the musculoskeletal system, the circadian clock regulates several functions such as maintenance of skeletal muscle phenotype (McCarthy et al, 2007 ) and bone metabolism (Qin et al, 2023 ). Previous studies using mice showed that BMAL1 and CLOCK directly regulate the circadian expression of MyoD , which is a master regulator of myogenesis (Andrews et al, 2010 ).…”

Section: A Link Between the Circadian Clock And Agingmentioning

confidence: 99%

Circadian regulation in aging: Implications for spaceflight and life on earth

et al. 2023

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Alterations in the circadian system are characteristic of aging on Earth. With the decline in physiological processes due to aging, several health concerns including vision loss, cardiovascular disorders, cognitive impairments, and muscle mass loss arise in elderly populations. Similar health risks are reported as “red flag” risks among astronauts during and after a long‐term Space exploration journey. However, little is known about the common molecular alterations underlying terrestrial aging and space‐related aging in astronauts, and controversial conclusions have been recently reported. In light of the regulatory role of the circadian clock in the maintenance of human health, we review here the overlapping role of the circadian clock both on aging on Earth and spaceflight with a focus on the four most affected systems: visual, cardiovascular, central nervous, and musculoskeletal systems. In this review, we briefly introduce the regulatory role of the circadian clock in specific cellular processes followed by alterations in those processes due to aging. We next summarize the known molecular alterations associated with spaceflight, highlighting involved clock‐regulated genes in space flown Drosophila, nematodes, small mammals, and astronauts. Finally, we discuss common genes that are altered in terms of their expression due to aging on Earth and spaceflight. Altogether, the data elaborated in this review strengthen our hypothesis regarding the timely need to include circadian dysregulation as an emerging hallmark of aging on Earth and beyond.

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Circadian clock genes as promising therapeutic targets for bone loss

Cited by 8 publications

References 106 publications

The specificities, influencing factors, and medical implications of bone circadian rhythms

The specificities, influencing factors, and medical implications of bone circadian rhythms

Circadian Regulation of Macrophages and Osteoclasts in Rheumatoid Arthritis

Circadian regulation in aging: Implications for spaceflight and life on earth

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