<scp>BMAL</scp>1 deficiency promotes skeletal mandibular hypoplasia via <scp>OPG</scp> downregulation

Zhou, Xin; Yu, Ran; Long, Yanlin; Zhao, Jiajia; Yu, Shaojun; Tang, Qingming; Chen, Lili

doi:10.1111/cpr.12470

Cited by 31 publications

(36 citation statements)

References 42 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In line with this, the protein-coding gene with the strongest downregulation was Aryl Hydrocarbon Receptor Nuclear Translocator Like (Arntl, Bmal, Bhlhe5), which is a circadian master regulator repressed by Per2. Arntl is associated with susceptibility to hypertension and diabetes and can activate the TNF receptor Osteoprotegerin [22][23][24]. Another strongly downregulated gene was Cadherin 11 (Cdh11), a calcium-dependent mediator of cell adhesion and cytoskeleton and inhibitor of Wnt and Rho activation [25].…”

Section: Resultsmentioning

confidence: 99%

Podocyte RNA sequencing reveals Wnt- and ECM-associated genes as central in FSGS

et al. 2020

View full text Add to dashboard Cite

Loss of podocyte differentiation can cause nephrotic-range proteinuria and Focal and Segmental Glomerulosclerosis (FSGS). As specific therapy is still lacking, FSGS frequently progresses to end-stage renal disease. The exact molecular mechanisms of FSGS and gene expression changes in podocytes are complex and widely unknown as marker changes have mostly been assessed on the glomerular level. To gain a better insight, we isolated podocytes of miR-193a overexpressing mice, which suffer from FSGS due to suppression of the podocyte master regulator Wt1. We characterised the podocytic gene expression changes by RNAseq and identified many novel candidate genes not linked to FSGS so far. This included strong upregulation of the receptor tyrosine kinase EphA6 and a massive dysregulation of circadian genes including the loss of the transcriptional activator Arntl. By comparison with podocyte-specific changes in other FSGS models we found a shared dysregulation of genes associated with the Wnt signaling cascade, while classical podocyte-specific genes appeared widely unaltered. An overlap with gene expression screens from human FSGS patients revealed a strong enrichment in genes associated with extracellular matrix (ECM) and metabolism. Our data suggest that FSGS progression might frequently depend on pathways that are often overlooked when considering podocyte homeostasis.

show abstract

Section: Resultsmentioning

confidence: 99%

Podocyte RNA sequencing reveals Wnt- and ECM-associated genes as central in FSGS

et al. 2020

View full text Add to dashboard Cite

show abstract

“…A large quantity of studies have suggested that circadian disruptions are closely associated with the formation and development of various diseases including cancer (Momma et al, 2017; Polo et al, 2017; Xiong et al, 2018), dysplasia (Vilches et al, 2014; Voiculescu et al, 2016; Zhao et al, 2018; Zhou et al, 2018), cardiovascular disease (Angelousi et al, 2018), obesity (Antunes et al, 2010), diabetes (Pan et al, 2011), and sleep disorder (Logan and McClung, 2019). As previously described, the cell cycle and the circadian clock are two basic periodic processes of a day, and they are interrelated.…”

Section: Circadian Rhythm Disorder and Diseasesmentioning

confidence: 99%

“…Furthermore, our previous studies showed the importance of the circadian clock on bone development. Circadian disruption resulted in Bmal1 down-regulation, leading to direct inhibition of Opg transcription (Zhou et al, 2018) and an indirect increase in Mmp3 expression through P65 phosphorylation (Zhao et al, 2018). These changes promoted osteoclasis and suppressed osteogenesis, resulting in bone loss and abnormal mandibular development.…”

Section: Circadian Rhythm Disorder and Diseasesmentioning

confidence: 99%

New Insights Into the Circadian Rhythm and Its Related Diseases

et al. 2019

Self Cite

View full text Add to dashboard Cite

Circadian rhythms (CR) are a series of endogenous autonomous oscillators generated by the molecular circadian clock which acting on coordinating internal time with the external environment in a 24-h daily cycle. The circadian clock system is a major regulatory factor for nearly all physiological activities and its disorder has severe consequences on human health. CR disruption is a common issue in modern society, and researches about people with jet lag or shift works have revealed that CR disruption can cause cognitive impairment, psychiatric illness, metabolic syndrome, dysplasia, and cancer. In this review, we summarized the synchronizers and the synchronization methods used in experimental research, and introduced CR monitoring and detection methods. Moreover, we evaluated conventional CR databases, and analyzed experiments that characterized the underlying causes of CR disorder. Finally, we further discussed the latest developments in understanding of CR disruption, and how it may be relevant to health and disease. Briefly, this review aimed to synthesize previous studies to aid in future studies of CR and CR-related diseases.

show abstract

“…Evidence indicates that GCs act directly and indirectly in bone tissue to cause osteoporosis [reviewed in 12]. However, we are aware of only a few studies [13], [14], [15], [18] on the interactions of bone with circadian clock genes. Moreover, the expression of clock genes in osteoblasts is regulated by the sympathetic nervous system and the hormone leptin, which regulates bone remodeling, a homeostatic function that maintains a constant bone mass [13].…”

Section: Introductionmentioning

confidence: 99%

“…Moreover, the expression of clock genes in osteoblasts is regulated by the sympathetic nervous system and the hormone leptin, which regulates bone remodeling, a homeostatic function that maintains a constant bone mass [13]. In homozygous Arntl/Bmal1 -deficient ( Arntl −/− ) mice, osteoclast differentiation is increased by downregulating the expression of osteoprotegerin [14]. Further, osteoclast-specific Arntl/Bmal1 -knockout mice have increased bone mass because of diminished osteoclast differentiation [15], and ARNTL/BMAL1-deficient osteoblasts have a higher ability compared with wild-type (WT) mice to support osteoclastogenesis by inducing the synthesis of RANKL, which is an endogenous osteoclast-activating factor secreted mainly by osteoblasts and activated T cells [16], [17].…”

Section: Introductionmentioning

confidence: 99%

The period circadian clock 2 gene responds to glucocorticoids and regulates osteogenic capacity

Abe

Sato

Yoda

et al. 2019

Regenerative Therapy

View full text Add to dashboard Cite

Introduction The central regulatory system that generates biological rhythms is regulated by circadian clock genes expressed by cells in the suprachiasmatic nucleus. Signals from this system are converted to adrenocortical hormones through the sympathetic nervous system and transmitted to peripheral organs. Another system releases glucocorticoids (GCs) in response to stress through the HPA-axis. Here we investigated the second messenger GC, which is shared by these systems and influences the expression of circadian clock genes of cells of the musculoskeletal system and in viable bone tissue. Methods We used mouse-derived cell lines, which differentiate into osteoblasts (MC3T3-E1, C2C12, and 10T1/2) as well as primary cultures of mouse osteoblasts to determine the expression levels of circadian clock genes that respond to GC. Mice (mPer2 m/m ) with an inactivating mutation in the period circadian clock 2 gene ( Per2 ) exhibit marked dysrhythmia. Here we compared the bone morphologies of mPer2 m/m mice with those of wild-type (WT) mice. Results The expression of major circadian clock genes was detected in each cell line, and their responsiveness to GC was confirmed. We focused on Per2 , a negative regulator of the circadian clock and found that a Per2 -loss-of-function mutation increased the proliferative capacity of osteoblasts. Treatment of mutant mice with slow-release GC and bisphosphonate affected the maturation of bone tissue, which reflects a tendency to retard calcification. Conclusion Our investigations of the mechanisms that regulate circadian rhythm function in tissues of the musculoskeletal system that respond to the stress hormone GC, reveal that Per2 is required for the maturation of bone tissue. Thus, the influences of the systems that control circadian rhythms and the responses to stress by regenerating tissue used for regenerative medicine must be considered and studied in greater detail.

show abstract

BMAL1 deficiency promotes skeletal mandibular hypoplasia via OPG downregulation

Abstract: These results indicate that the circadian clock plays a critical role in the growth and development of mandible by regulating OPG expression, and present a potential therapeutic strategy to prevent SMH.

Cited by 31 publications

References 42 publications

Podocyte RNA sequencing reveals Wnt- and ECM-associated genes as central in FSGS

Podocyte RNA sequencing reveals Wnt- and ECM-associated genes as central in FSGS

New Insights Into the Circadian Rhythm and Its Related Diseases

The period circadian clock 2 gene responds to glucocorticoids and regulates osteogenic capacity

Contact Info

Product

Resources

About