Aging alters bone-fat reciprocity by shifting in vivo mesenchymal precursor cell fate towards an adipogenic lineage.
Aging alters bone-fat reciprocity by shifting in vivo mesenchymal precursor cell fate towards an adipogenic lineage.
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DOI：
10.1016/j.bone.2016.01.014
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发表时间：
2016-04
期刊：
影响因子：
4.1
通讯作者：
Pignolo RJ
中科院分区：
文献类型：
--
作者：
Singh L;Brennan TA;Russell E;Kim JH;Chen Q;Brad Johnson F;Pignolo RJ
骨髓间充质祖细胞（MPCs）在维持骨平衡中起重要作用。骨骼发生与年龄相关的变化，导致骨密度下降和脂肪含量相对增加。尽管体外研究表明成骨和成脂命运之间存在年龄相关的谱系转换，但干细胞和微环境对这一过程的贡献尚未在体内阐明。为了研究MPC和微环境老化对功能移植和谱系转换的影响，在非清髓性条件下在老年受体中进行移植研究，供体MPC来自年轻和老年绿色荧光蛋白（GFP）转基因小鼠。在年轻受体的骨髓、骨衬区域和基质中观察到年轻MPC或其后代的稳健植入;然而，在移植有老年MPC的老年受体的相同部位观察到显著较低的植入。无论MPC供体年龄如何，移植MPC的分化都强烈支持老年受体的脂肪生成而不是骨生成，这表明随着体内衰老而发生的微环境改变主要是MPC谱系转换的原因。这些数据表明，衰老改变了骨-脂肪的相互作用和间充质祖细胞向成脂命运的分化。
Bone marrow derived mesenchymal progenitor cells (MPCs) play an important role in bone homeostasis. Age-related changes occur in bone resulting in a decrease in bone density and a relative increase in adipocity. Although in vitro studies suggest the existence of an age-related lineage switch between osteogenic and adipogenic fates, stem cell and microenvironmental contributions to this process have not been elucidated in vivo. In order to study the effects of MPC and microenvironmental aging on functional engraftment and lineage switching, transplantation studies were performed under non-myeloablative conditions in old recipients, with donor MPCs derived from young and old green fluorescent protein (GFP) transgenic mice. Robust engraftment by young MPCs or their progeny was observed in the marrow, bone-lining region and in the matrix of young recipients; however, significantly lower engraftment was seen at the same sites in old recipients transplanted with old MPCs. Differentiation of transplanted MPCs strongly favored adipogenesis over osteogenesis in old recipients irrespective of MPC donor age, suggesting that microenvironmental alterations that occur with in vivo aging are predominately responsible for MPC lineage switching. These data indicate that aging alters bone-fat reciprocity and differentiation of mesenchymal progenitors toward an adipogenic fate.