Bmal1 induces osteoblast differentiation via regulation of BMP2 expression in MC3T3-E1 cells

Min, Hyeon-Young; Kim, Kyeong-Min; Wee, Gabbine; Kim, Eun-Jung; Jang, Won‐Gu

doi:10.1016/j.lfs.2016.08.002

Cited by 22 publications

(17 citation statements)

References 26 publications

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“…BMAL1 is a core component that plays critical roles in generating and maintaining circadian rhythm ( Lipton et al., 2015 ). BMAL1 deficiency had a broad impact on bone deformity, which is consistent with the previous reports ( Min et al., 2016 , Samsa et al., 2016 ). Consistently, we observed that juvenile SMH patients had decreased BMAL1 expression in their mandibular tissues.…”

Section: Discussionsupporting

confidence: 92%

“…We found that MMP3 was upregulated in mandibular tissues of juvenile SMH patients. The previous study reported that BMAL1 promotes osteoblast differentiation by upregulating BMP2 expression, indicating the correlation of BMAL1 with osteoblast differentiation regulators ( Min et al., 2016 ). Together these results highlight the complex mechanism of circadian-rhythm-related bone developmental processes.…”

Section: Discussionmentioning

confidence: 90%

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BMAL1 Deficiency Contributes to Mandibular Dysplasia by Upregulating MMP3

et al. 2018

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SummarySkeletal mandibular hypoplasia (SMH), one of the common types of craniofacial deformities, seriously affects appearance, chewing, pronunciation, and breathing. Moreover, SMH is prone to inducing obstructive sleep apnea syndrome. We found that brain and muscle ARNT-like 1 (BMAL1), the core component of the molecular circadian oscillator, was significantly decreased in mandibles of juvenile SMH patients. Accordingly, SMH was observed in circadian-rhythm-disrupted or BMAL1-deficient mice. RNA sequencing and protein chip analyses suggested that matrix metallopeptidase 3 (MMP3) is the potential target of BMAL1. Interestingly, in juvenile SMH patients, we observed that MMP3 was obviously increased. Consistently, MMP3 was upregulated during the whole growth period of 3–10 weeks in Bmal1−/− mice. Given these findings, we set out to characterize the underlying mechanism and found BMAL1 deficiency enhanced Mmp3 transcription through activating p65 phosphorylation. Together, our results provide insight into the mechanism by which BMAL1 is implicated in the pathogenesis of SMH.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 90%

BMAL1 Deficiency Contributes to Mandibular Dysplasia by Upregulating MMP3

et al. 2018

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“…36,65,66 These data suggest that osteoblastic gene expression occurs at the molecular level and likely via a clock-mediated process. Regarding their specific functions in bone-mediated processes, Per and Cry are important negative regulators of bone, whereas Bmal is a positive regulator of bone 188,[199][200][201] (Figures 1B and S1). As would be expected, a disruption in one's circadian rhythm could lead to adverse effects on bone physiology.…”

Section: Circadian Disruption Related Bone Lossmentioning

confidence: 99%

Melatonin effects on bone: Implications for use as a therapy for managing bone loss

Munmun

Witt‐Enderby

2021

Journal of Pineal Research

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Melatonin is the primary circadian output signal from the brain and is mainly synthesized in pinealocytes. The rhythm and secretion of melatonin are under the control of an endogenous oscillator located in the SCN or the master biological clock.Disruptions in circadian rhythms by shift work, aging, or light at night are associated with bone loss and increased fracture risk. Restoration of nocturnal melatonin peaks to normal levels or therapeutic levels through timed melatonin supplementation has been demonstrated to provide bone-protective actions in various models. Melatonin is a unique molecule with diverse molecular actions targeting melatonin receptors located on the plasma membrane or mitochondria or acting independently of receptors through its actions as an antioxidant or free radical scavenger to stimulate osteoblastogenesis, inhibit osteoclastogenesis, and improve bone density. Its additional actions on entraining circadian rhythms and improving quality of life in an aging population coupled with its safety profile make it an ideal therapeutic candidate for protecting against bone loss in susceptible populations. The intent of this review is to provide a focused discussion on bone loss and disorders of the bone as it relates to melatonin and conditions that modify melatonin levels with the hope that future therapies include those that include melatonin and correct those factors that modify melatonin levels like circadian disruption.

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“…Our previous study and the research of Li et al demonstrated that Bmal1 may regulate bone formation via the Wnt/ β -catenin pathway and that glycogen synthase kinase-3 β (GSK-3 β ) may act as the medium and link between Bmal1 and the Wnt/ β -catenin pathway [ 19 , 20 ]. Min et al showed that Bmal1 may promote osteogenic differentiation by regulating the expression of BMP2 in MC3T3-E1 cells [ 21 ]. In regard to the relationship between Bmal1 and bone formation, their results seem to be different from those of this present study.…”

Section: Discussionmentioning

confidence: 99%

The Interaction between Bmal1 and Per2 in Mouse BMSC Osteogenic Differentiation

Zhuo

Wang

Zhao

2018

Stem Cells International

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The circadian clock is a system that controls endogenous time of organisms, and it regulates the physiology and behavior of bodies. The transcription factors Brain and Muscle ARNT-like Protein 1 (BMAL1) and Period2 (Per2) are components of the circadian clock, and they play vital roles in circadian clock function. Both Bmal1−/− mice and Per2−/− mice display obvious bone volume changes. In this study, we inhibited the expression of Bmal1 in bone marrow-derived mesenchymal stem cells (BMSCs) using a lentiviral vector harboring RNAi sequences, which increased the osteogenic differentiation capability of BMSCs. We also suppressed Per2 gene expression using an adenovirus vector harboring RNAi sequences, and similarly, the osteogenic differentiation ability of BMSCs was enhanced. Furthermore, when both Bmal1 and Per2 gene expression was suppressed in BMSCs by lentiviral and adenoviral interference, the osteogenic differentiation capability was stronger than that in BMSCs following single-gene inhibition. Our data support that both Bmal1 and Per2 play negative roles in BMSC osteogenic differentiation and that Bmal1 and Per2 have a synergistic effect on the osteogenic differentiation of BMSCs.

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Bmal1 induces osteoblast differentiation via regulation of BMP2 expression in MC3T3-E1 cells

Cited by 22 publications

References 26 publications

BMAL1 Deficiency Contributes to Mandibular Dysplasia by Upregulating MMP3

BMAL1 Deficiency Contributes to Mandibular Dysplasia by Upregulating MMP3

Melatonin effects on bone: Implications for use as a therapy for managing bone loss

The Interaction between Bmal1 and Per2 in Mouse BMSC Osteogenic Differentiation

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