Identification of a subpopulation of marrow MSC-derived medullary adipocytes that express osteoclast-regulating molecules: marrow adipocytes express osteoclast mediators.

Identification of a subpopulation of marrow MSC-derived medullary adipocytes that express osteoclast-regulating molecules: marrow adipocytes express osteoclast mediators.
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DOI:
10.1371/journal.pone.0108920
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发表时间:
2014
期刊:
影响因子:
3.7
通讯作者:
Haynesworth SE
Haynesworth SE
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Holt V;Caplan AI;Haynesworth SE

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老年性骨质疏松症的一个共同特征是骨髓髓质脂肪生成增加和骨密度降低。在这项研究中,我们调查了髓脂肪细胞谱系的细胞是否有可能直接支持破骨细胞的形成,破骨细胞在骨中的活性导致骨降解。采用体外间充质干细胞(MSC)衍生的髓样脂肪细胞谱系培养模型研究重要破骨细胞介质RANKL、M-CSF、SDF-1和OPG的表达。我们进一步评估了特定发育阶段的脂肪细胞是否能够在培养中支持破骨细胞样细胞的形成。体外MSC衍生的髓质脂肪细胞显示M-CSF、RANKL和OPG的mRNA和蛋白表达谱依赖于其发育/代谢阶段。此外,在不同谱系阶段的MSC衍生脂肪细胞中观察到RANKL表达,这些细胞也能够在与外周血单核细胞共培养中支持破骨细胞样细胞形成。这些结果表明,骨髓脂肪细胞和破骨细胞的形成之间的联系在体内,并可能有重大意义的老年性骨质疏松症的骨密度降低的机制。
Increased marrow medullary adipogenesis and an associated decrease in bone mineral density, usually observed in elderly individuals, is a common characteristic in senile osteoporosis. In this study we investigated whether cells of the medullary adipocyte lineage have the potential to directly support the formation of osteoclasts, whose activity in bone leads to bone degradation. An in vitro mesenchymal stem cell (MSC)-derived medullary adipocyte lineage culture model was used to study the expression of the important osteoclast mediators RANKL, M-CSF, SDF-1, and OPG. We further assessed whether adipocytes at a specific developmental stage were capable of supporting osteoclast-like cell formation in culture. In vitro MSC-derived medullary adipocytes showed an mRNA and protein expression profile of M-CSF, RANKL, and OPG that was dependent on its developmental/metabolic stage. Furthermore, RANKL expression was observed in MSC-derived adipocytes that were at a distinct lineage stage and these cells were also capable of supporting osteoclast-like cell formation in co-cultures with peripheral blood mononuclear cells. These results suggest a connection between medullary adipocytes and osteoclast formation in vivo and may have major significance in regards to the mechanisms of decreased bone density in senile osteoporosis.
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