Division of Allergy, Immunology, and Rheumatology, School of Medicine and Dentistry, University of Rochester, Rochester, New York, USA.
Department of Environmental Medicine, School of Medicine and Dentistry, University of Rochester, Rochester, New York, USA.
FASEB J. 2018 Jun;32(6):3174-3183. doi: 10.1096/fj.201701379R. Epub 2018 Jan 17.
Thy1 (CD90), a glycosylated, glycophosphatidylinositol-anchored membrane protein highly expressed by subsets of mesenchymal stem cells and fibroblasts, inhibits adipogenesis. The role of Thy1 on bone structure and function has been poorly studied and represents a major knowledge gap. Therefore, we analyzed the long bones of wild-type (WT) and Thy1 knockout (KO) mice with micro-computed tomography (micro-CT) and histomorphometry to compare changes in bone architecture and overall bone structure. micro-CT analysis of long bones revealed Thy1 KO and WT mice fed a high-fat diet demonstrated bone structural parameters at 4 mo that differed significantly between WT and KO mice. A significant reduction in trabecular bone volume was noted in Thy1 KO mice. The most prominent differences were observed in trabecular bone volume ratio and trabecular bone connectivity density. Consistent with micro-CT measurements, histomorphometric analysis also showed decreased bone volume in the obese Thy1 KO mice compared to obese WT mice. In vitro assays revealed that osteogenic conditions increased Thy1 expression during OB differentiation and absence of Thy1 attenuated osteoblastogenesis. Together, these findings support the concept that Thy1 serves as a major mechanistic link to regulate bone formation and negatively regulate adipogenesis.-Paine, A., Woeller, C. F., Zhang, H., Garcia-Hernandez, M. L., Huertas, N., Xing, L., Phipps, R. P., Ritchlin, C. T. Thy1 is a positive regulator of osteoblast differentiation and modulates bone homeostasis in obese mice.
Thy1（CD90）是一种糖基化的糖磷脂酰肌醇锚定膜蛋白，在间充质干细胞和成纤维细胞的亚群中高度表达，可抑制脂肪生成。Thy1 对骨结构和功能的作用尚未得到充分研究，这是一个主要的知识空白。因此，我们使用微计算机断层扫描（micro-CT）和组织形态计量学分析了野生型（WT）和 Thy1 敲除（KO）小鼠的长骨，以比较骨结构和整体骨结构的变化。长骨的 micro-CT 分析显示，高脂饮食喂养的 Thy1 KO 和 WT 小鼠在 4 个月时的骨结构参数与 WT 和 KO 小鼠之间存在显著差异。Thy1 KO 小鼠的小梁骨体积明显减少。最显著的差异观察到在小梁骨体积比和小梁骨连接密度。与 micro-CT 测量结果一致，组织形态计量学分析也显示肥胖 Thy1 KO 小鼠的骨体积较肥胖 WT 小鼠减少。体外实验表明，成骨条件下 OB 分化过程中 Thy1 表达增加，而 Thy1 缺失则减弱成骨细胞生成。综上所述，这些发现支持 Thy1 作为调节骨形成和负向调节脂肪生成的主要机制联系的概念。-Paine，A.，Woeller，C. F.，Zhang，H.，Garcia-Hernandez，M. L.，Huertas，N.，Xing，L.，Phipps，R. P.，Ritchlin，C. T. Thy1 是成骨细胞分化的正调节剂，并调节肥胖小鼠的骨稳态。
