PGC-1α Controls Skeletal Stem Cell Fate and Bone-Fat Balance in Osteoporosis and Skeletal Aging by Inducing TAZ.
PGC-1α Controls Skeletal Stem Cell Fate and Bone-Fat Balance in Osteoporosis and Skeletal Aging by Inducing TAZ.
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DOI：
10.1016/j.stem.2018.09.001
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发表时间：
2018-10-04
期刊：
影响因子：
23.9
通讯作者：
Wang CY
中科院分区：
文献类型：
--
作者：
Yu B;Huo L;Liu Y;Deng P;Szymanski J;Li J;Luo X;Hong C;Lin J;Wang CY
骨骼干细胞（SSC）的异常谱系特化导致骨质疏松和骨骼衰老中骨量减少和骨髓脂肪组织（MAT）增加。虽然成骨细胞和脂肪形成谱系的主要调节因子已经被确定，但对与MAT积累和骨质疏松性骨丢失相关的因素知之甚少。在这里，我们确定过氧化物酶体增殖物激活受体γ共激活因子1-α（PGC-1α）作为细胞命运决定的关键开关，其表达随着人类和小鼠SSC的衰老而减少。PGC-1α的缺失促进了小鼠SSCs的成脂分化，但成骨分化受到损害。SSC中PGC-1α的缺失损害了骨形成，间接促进了骨吸收，同时增强了MAT的积累。相反，PGC-1α的诱导减弱了骨质疏松性骨丢失和MAT积累。机制上，PGC-1α通过诱导TAZ维持骨和脂肪平衡。我们的研究结果表明，PGC-1α是一个潜在的重要的治疗靶点，在骨质疏松症和骨骼老化的治疗。
Aberrant lineage specification of skeletal stem cells (SSCs) contributes to reduced bone mass and increased marrow adipose tissue (MAT) in osteoporosis and skeletal aging. Although master regulators of osteoblastic and adipogenic lineages have been identified, little is known about factors that are associated with MAT accumulation and osteoporotic bone loss. Here, we identify peroxisome-proliferator-activated receptor γ coactivator 1-α (PGC-1α) as a critical switch of cell fate decisions whose expression decreases with aging in human and mouse SSCs. Loss of PGC-1α promoted adipogenic differentiation of murine SSCs at the expense of osteoblastic differentiation. Deletion of PGC-1α in SSCs impaired bone formation and indirectly promoted bone resorption while enhancing MAT accumulation. Conversely, induction of PGC-1α attenuated osteoporotic bone loss and MAT accumulation. Mechanistically, PGC-1α maintains bone and fat balance by inducing TAZ. Our results suggest that PGC-1α is a potentially important therapeutic target in the treatment of osteoporosis and skeletal aging.
影响因子：
23.9
作者：
Yu B;Huo L;Liu Y;Deng P;Szymanski J;Li J;Luo X;Hong C;Lin J;Wang CY
通讯作者：
Wang CY