Roles of brain and muscle <scp>ARNT</scp>‐like 1 and Wnt antagonist Dkk1 during osteogenesis of bone marrow stromal cells

He, Yuting; Chen, Y; Zhao, Qing; Tan, Zhi

doi:10.1111/cpr.12075

Cited by 28 publications

(27 citation statements)

References 38 publications

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“…Disruption of the Period genes results in a high bone mass due increased osteoblast proliferation in a systemic manner acting through the molecular clock in osteoblasts, whereas disruption of Bmal1 results in a low bone mass in a call autonomous manner resulting from a depletion of osteoprogenitors and their reduced ability to differentiate into osteoblasts and deposit bone matrix. This model is supported by recent observations that the reduced capacity of marrow stromal cells from aged mice to proliferate correlates with decreased mRNA and protein levels of BMAL1, while BMAL1 deficiency results in an increase in the number of senescent cells in different tissues, including bone marrow stromal cells (Chen et al, 2012; Lin et al, 2013; Khapre et al, 2011; He et al, 2013). Further experiments using conditional, tissue specific knock outs are needed to dissect systemic and cell autonomous mechanisms of the circadian clock and BMAL1 dependent control of bone formation.…”

Section: 0 Discussionsupporting

confidence: 65%

Deficiency of circadian clock protein BMAL1 in mice results in a low bone mass phenotype

Samsa

Vasanji

Midura

et al. 2016

Bone

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The circadian clock is an endogenous time keeping system that controls the physiology and behavior of many organisms. The transcription factor Brain and Muscle ARNT-like Protein 1 (BMAL1) is a component of the circadian clock and necessary for clock function. Bmal1−/− mice display accelerated aging and many accompanying age associated pathologies. Here, we report that mice deficient for BMAL1 have a low bone mass phenotype that is absent at birth and progressively worsens over their lifespan. Accelerated aging of these mice is associated with the formation of bony bridges occurring across the metaphysis to the epiphysis, resulting in shorter long bones. Using micro-computed tomography we show that Bmal1−/− mice have reductions in cortical and trabecular bone volume and other micro-structural parameters and a lower bone mineral density. Histology shows a deficiency of BMAL1 results in a reduced number of active osteoblasts and osteocytes in vivo. Isolation of bone marrow derived mesenchymal stem cells from Bmal1−/− mice demonstrate a reduced ability to differentiate into osteoblasts in vitro, which likely explains the observed reductions in osteoblasts and osteocytes, and may contribute to the observed osteopenia. Our data support the role of the circadian clock in the regulation of bone homeostasis and shows that BMAL1 deficiency results in a low bone mass phenotype.

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Section: 0 Discussionsupporting

confidence: 65%

Deficiency of circadian clock protein BMAL1 in mice results in a low bone mass phenotype

Samsa

Vasanji

Midura

et al. 2016

Bone

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“…Thus, investigation of the disordered mechanism of osteogenic differentiation in BMScs and development of effective methods of prevention and early therapy are crucial. a number of previous studies have reported that osteogenic differentiation-related genes are expressed periodically (5,6). Brain and muscle arnT-like 1 (BMal1) is the most important component of the molecular biological clock, expression of which has been found to have 24-h periodicity in bone.…”

Section: Introductionmentioning

confidence: 99%

Icariin promotes osteogenic differentiation of BMSCs by upregulating BMAL1 expression via BMP signaling

Huang

Wei

et al. 2020

Mol Med Report

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increasing research has demonstrated that expression of brain and muscle arnT-like 1 (BMal1) and other circadian clock genes can be regulated by drugs and toxicants. We previously demonstrated that icariin, extracted from Herba epimedii, sromotes osteogenic differentiation. However, the mechanism underlying the association between icariin and BMal1 in osteogenic differentiation of bone marrow-derived mesenchymal stem cells (BMScs) remains unclear. The present study was designed with an aim to clarify the association between icariin and BMal1 in osteogenic differentiation of BMScs. The cell counting Kit-8 assay was used to evaluate cell proliferation. The expression of bone morphogenetic protein 2 (BMP2), runX family transcription factor 2 (runX2), alkaline phosphatase (alP), osteocalcin (oc) and BMal1 in BMScs was evaluated by reverse transcription-quantitative Pcr and western blotting. alP and alizarin red S (arS) staining were also performed. icariin promoted BMSc proliferation, and upregulated expression of osteogenic genes and BMal1. in addition, expression of the osteogenic genes BMP2, runX2, alP and oc were upregulated by BMal1 overexpression. Furthermore, we confirmed that BMal1 deficiency suppressed osteogenic differentiation in BMScs. Finally, arS staining of BMal1 -/-BMScs revealed that BMal1 was an essential intermediary in matrix mineralization during osteogenic differentiation. in conclusion, these results demonstrated that icariin promoted osteogenic differentiation through BMal1-BMP2 signaling in BMScs. The present study thus described a novel target of icariin that has potential applications in the treatment of osteogenic disorders.

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“…Overexpression of Bmal1 could promote bone mesenchymal stem cell (BMSC) proliferation, and this process was relatively independent of Bmal1 regulation of circadian rhythm, testifying that Bmal1 could inhibit cell aging [12]. Furthermore, the expression of b-catenin, the key factor of Wnt/b-catenin signaling, increased when Bmal1 was overexpressed [13], and another study showed that b-catenin expression decreased with aging [14]. As the main signaling pathway in development, Wnt/b-catenin signaling may play vital roles in the aging process [15,16].…”

Section: Introductionmentioning

confidence: 99%

Overexpression of the Circadian Clock Gene Rev-erbα Affects Murine Bone Mesenchymal Stem Cell Proliferation and Osteogenesis

Lin

Chen

et al. 2015

Stem Cells and Development

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Bone mesenchymal stem cell (BMSC) age-related changes include decreased osteogenesis and increased adipogenesis. Rev-erba and the Wnt/b-catenin signaling pathway were known to play important roles in BMSC aging. In this study, we have aimed to elucidate whether Rev-erba and Wnt/b-catenin signaling interact during BMSC proliferation and osteogenesis. Our results showed that Rev-erba expression gradually dropped during BMSC osteogenesis, and overexpression of Rev-erba in BMSCs inhibited cell proliferation and osteogenesis. The inhibition of cell proliferation induced by Rev-erba overexpression was partially reversed when Wnt/bcatenin signaling was activated. These results suggested that Rev-erba could promote BMSC aging and may be the negative regulator during the late stage of osteogenesis. The clock gene Rev-erba and Wnt/b-catenin signaling interact in the regulation of cell proliferation.

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Roles of brain and muscle ARNT‐like 1 and Wnt antagonist Dkk1 during osteogenesis of bone marrow stromal cells

Abstract: These findings demonstrated that Bmal1 and Wnt signalling may have a synergistic effect at a particular stage of osteogenesis. Inhibition of Wnt signalling did not greatly affect ageing of MSCs through early passages.

Cited by 28 publications

References 38 publications

Deficiency of circadian clock protein BMAL1 in mice results in a low bone mass phenotype

Deficiency of circadian clock protein BMAL1 in mice results in a low bone mass phenotype

Icariin promotes osteogenic differentiation of BMSCs by upregulating BMAL1 expression via BMP signaling

Overexpression of the Circadian Clock Gene Rev-erbα Affects Murine Bone Mesenchymal Stem Cell Proliferation and Osteogenesis

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