Thy-1 (CD90) promotes bone formation and protects against obesity
Thy-1 (CD90) promotes bone formation and protects against obesity
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DOI：
10.1126/scitranslmed.aao6806
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发表时间：
2018-08-08
影响因子：
17.1
通讯作者：
Saalbach, Anja
中科院分区：
文献类型：
--
作者：
Picke, Ann-Kristin;Campbell, Graeme M.;Saalbach, Anja
骨质疏松和肥胖是成骨和脂肪分化紊乱的结果，是老龄化社会面临的新挑战。由于Thy-1在间充质成纤维细胞中的调节作用，我们研究了Thy-1表达对成骨和成脂分化间充质干细胞（MSC）命运的影响，以及对体内骨形成和脂肪组织发育的影响。与野生型小鼠的骨髓间充质干细胞相比，来自thy -1缺失小鼠的骨髓间充质干细胞的成骨细胞分化减少，成脂分化增加。一致地，thy -1缺陷小鼠表现出骨体积和骨形成率下降，皮质孔隙率升高，导致骨强度降低。同时，体重、皮下/外阴脂肪量和骨脂肪体积增加。它们-1缺乏伴随着特异性Wnt配体的表达减少，同时Wnt抑制剂sclerostin和dickkopf-1的表达增加，以及对Wnt的反应性改变。我们证明骨质疏松症患者的骨重塑紊乱和肥胖患者的脂肪组织积累失调反映了血清中Thy-1浓度的降低。我们的发现为骨形成和肥胖的相互调节提供了新的见解，并为监测和干预肥胖和骨质疏松症中脂肪生成和成骨平衡失调开辟了新的视角。
Osteoporosis and obesity result from disturbed osteogenic and adipogenic differentiation and present emerging challenges for our aging society. Because of the regulatory role of Thy-1 in mesenchyme-derived fibroblasts, we investigated the impact of Thy-1 expression on mesenchymal stem cell (MSC) fate between osteogenic and adipogenic differentiation and consequences for bone formation and adipose tissue development in vivo. MSCs from Thy-1-deficient mice have decreased osteoblast differentiation and increased adipogenic differentiation compared to MSCs from wild-type mice. Consistently, Thy-1-deficient mice exhibited decreased bone volume and bone formation rate with elevated cortical porosity, resulting in lower bone strength. In parallel, body weight, subcutaneous/epigonadal fat mass, and bone fat volume were increased. Thy-1 deficiency was accompanied by reduced expression of specific Wnt ligands with simultaneous increase of the Wnt inhibitors sclerostin and dickkopf-1 and an altered responsiveness to Wnt. We demonstrated that disturbed bone remodeling in osteoporosis and dysregulated adipose tissue accumulation in patients with obesity were mirrored by reduced serum Thy-1 concentrations. Our findings provide new insights into the mutual regulation of bone formation and obesity and open new perspectives to monitor and to interfere with the dysregulated balance of adipogenesis and osteogenesis in obesity and osteoporosis.