Department of Orthopedics, The Eighth Affiliated Hospital, Sun Yat-sen University, Shenzhen, China.
Department of Orthopedics, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China.
Elife. 2020 Oct 2;9:e59079. doi: 10.7554/eLife.59079.
Osteoporosis is a common systemic skeletal disorder resulting in bone fragility and increased fracture risk. It is still necessary to explore its detailed mechanisms and identify novel targets for the treatment of osteoporosis. Previously, we found that a lncRNA named in human could negatively regulate the lipoblast/adipocyte differentiation. However, it is still unclear whether affects osteoblast differentiation and whether is associated with osteoporosis. Our current research found that was decreased in the bones and BMSCs, a major origin of osteoblast, of osteoporosis patients. Mechanistically, promotes the osteoblast differentiation by interacting with UPF1 to degrade mRNA. Moreover, a decreased bone mass and impaired bone repair ability were observed in heterozygous mice, manifesting in osteoporosis. The systemic supplement of -overexpressing adenoviruses significantly ameliorated bone loss in an osteoporosis mouse model. In conclusion, promotes osteoblast differentiation by targeting the UPF1/SMAD7 axis and protects against osteoporosis.
骨质疏松症是一种常见的全身性骨骼疾病，导致骨骼脆弱和骨折风险增加。仍有必要探索其详细机制，并确定骨质疏松症的新治疗靶点。此前，我们发现一个名为 的长链非编码 RNA（lncRNA）可负向调控脂肪母细胞/脂肪细胞分化。然而， 是否影响成骨细胞分化以及 是否与骨质疏松症相关仍不清楚。我们目前的研究发现，骨质疏松症患者的骨骼和骨髓间充质干细胞（成骨细胞的主要来源）中的 表达降低。在机制上， 通过与 UPF1 相互作用降解 mRNA 来促进成骨细胞分化。此外，杂合子小鼠表现出骨量减少和骨修复能力受损，表现为骨质疏松症。系统补充过表达 的腺病毒显著改善了骨质疏松症小鼠模型的骨丢失。总之， 通过靶向 UPF1/SMAD7 轴促进成骨细胞分化，并预防骨质疏松症。
