Adipocytes Derived from Human Bone Marrow Mesenchymal Stem Cells Exert Inhibitory Effects on Osteoblastogenesis

Zhang, H.; Lu, W.; Zhao, Yuan; Rong, Peijing; Cao, Renhai; Gu, Wei; Xiao, Jingwen; Miao, Dengshun; Recker, Robert R.; Xiao, Gary Guishan

doi:10.2174/156652411796268704

Cited by 22 publications

(16 citation statements)

References 49 publications

(70 reference statements)

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“…Osteoblasts and adipocytes are derived from stromal cell progenitors and it has been inferred that adipocyte differentiation within the bone marrow reduces, or even precludes, concurrent osteoblast differentiation leading to bone loss [7, 10, 30–36]. Our observation that bone marrow adipocyte-deficient kit W/W-v mice have increased osteoblast perimeter is consistent with the view that low levels of adipogenesis increase osteoblast differentiation.…”

Section: Discussionsupporting

confidence: 90%

Failure to generate bone marrow adipocytes does not protect mice from ovariectomy-induced osteopenia

Iwaniec

Turner

2013

Bone

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A reciprocal association between bone marrow fat and bone mass has been reported in ovariectomized rodents, suggesting that bone marrow adipogenesis has a negative effect on bone growth and turnover balance. Mice with loss of function mutations in kit receptor (kitW/W-v) have no bone marrow adipocytes in tibia or lumbar vertebra. We therefore tested the hypothesis that marrow fat contributes to development of osteopenia by comparing the skeletal response to ovariectomy (ovx) in growing wild type (WT) and bone marrow adipocyte-deficient kitW/W-v mice. Mice were ovx at 4 weeks of age and sacrificed 4 or 10 weeks post-surgery. Body composition was measured at necropsy by dual-energy X-ray absorptiometry. Cortical (tibia) and cancellous (tibia and lumbar vertebra) bone architecture were evaluated by microcomputed tomography. Bone marrow adipocyte size and density, osteoblast- and osteoclast-lined bone perimeters, and bone formation were determined by histomorphometry. Ovx resulted in an increase in total body fat mass at 10 weeks post-ovx in both genotypes, but the response was attenuated in the in kitW/W-v mice. Adipocytes were present in bone marrow of tibia and lumbar vertebra in WT mice and bone marrow adiposity increased following ovx. In contrast, marrow adipocytes were not detected in either intact or ovx kitW/W-v mice. However, ovx in WT and kitW/W-v mice resulted in statistically indistinguishable changes in cortical and cancellous bone mass, cortical and cancellous bone formation rate, and cancellous osteoblast and osteoclast-lined bone perimeters. In conclusion, our findings do not support a causal role for increased bone marrow fat as a mediator of ovx-induced osteopenia in mice.

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Section: Discussionsupporting

confidence: 90%

Failure to generate bone marrow adipocytes does not protect mice from ovariectomy-induced osteopenia

Iwaniec

Turner

2013

Bone

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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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“…Mesenchymal stromal cells (MSC) residing in the marrow space give rise to cellular populations of the marrow microenvironment, such as osteoblasts and adipocytes. Because of their pluripotent capability, there has long been an assumption MSC phenotype directly influences bone – related parameters, i.e., increasing marrow adipogenesis is inversely proportional with bone mass [7]–[10]. MSCs additionally act as key regulators of hematopoiesis.…”

Section: Introductionmentioning

confidence: 99%

The Influence of Therapeutic Radiation on the Patterns of Bone Marrow in Ovary-Intact and Ovariectomized Mice

et al. 2012

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BackgroundThe functional components of bone marrow (i.e., the hematopoietic and stromal populations) and the adjacent bone have traditionally been evaluated incompletely as distinct entities rather than the integrated system. We perturbed this system in vivo using a medically relevant radiation model in the presence or absence of ovarian function to understand integrated tissue interaction.Methodology/Principal FindingsOvary-intact and ovariectomized mice underwent either no radiation or single fractional 16 Gy radiation to the caudal skeleton (I±R, OVX±R). Marrow fat, hematopoietic cellularity, and cancellous bone volume fraction (BV/TV %) were assessed. Ovariectomy alone did not significantly reduce marrow cellularity in non-irradiated mice (OVX−R vs. I−R, p = 0.8445) after 30 days; however it impaired the hematopoietic recovery of marrow following radiation exposure (OVX+R vs. I+R, p = 0.0092). The combination of radiation and OVX dramatically increases marrow fat compared to either factor alone (p = 0.0062). The synergistic effect was also apparent in the reduction of hematopoietic marrow cellularity (p = 0.0661); however it was absent in BV/TV% changes (p = 0.2520). The expected inverse relationship between marrow adiposity vs. hematopoietic cellularity and bone volume was observed. Interestingly compared with OVX mice, intact mice demonstrated double the reduction in hematopoietic cellularity and a tenfold greater degree of bone loss for a given unit of expansion in marrow fat.Conclusions/SignificanceOvariectomy prior to delivery of a clinically-relevant focal radiation exposure in mice, exacerbated post-radiation adipose accumulation in the marrow space but blunted bone loss and hematopoietic suppression. In the normally coupled homeostatic relationship between the bone and marrow domains, OVX appears to alter feedback mechanisms. Confirmation of this non-linear phenomenon (presumably due to differential radiosensitivity) and demonstration of the mechanism of action is needed to provide strategies to diminish the effect of radiation on exposed tissues.

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Adipocytes Derived from Human Bone Marrow Mesenchymal Stem Cells Exert Inhibitory Effects on Osteoblastogenesis

Cited by 22 publications

References 49 publications

Failure to generate bone marrow adipocytes does not protect mice from ovariectomy-induced osteopenia

Failure to generate bone marrow adipocytes does not protect mice from ovariectomy-induced osteopenia

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

The Influence of Therapeutic Radiation on the Patterns of Bone Marrow in Ovary-Intact and Ovariectomized Mice

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