Zhao Haoyang, Yang Mengfan, Liu Yujiao, Tu Xiaolin, Shao Gaohai
Key Laboratory of Diagnostic Medicine Designated by the Chinese Ministry of Education, College of Laboratory Medicine, Chongqing Medical University, Chongqing, 400016, China.
Department of Orthopedics, Affiliated Yongchuan Hospital of Chongqing Medical University, Chongqing, 402160, China.
NPJ Microgravity. 2025 Aug 1;11(1):50. doi: 10.1038/s41526-025-00510-y.
Disuse osteoporosis, caused by mechanical unloading, is linked to dysregulated TGFβ and BMP signaling. This study explores their roles and evaluates BMP9 as a potential therapy. A hindlimb unloading (HLU) mouse model was used to assess bone changes and signaling alterations. In vitro, a Rotary Cell Culture System (RCCS) with 3D printing simulated microgravity. BMP9 was overexpressed in bone marrow stromal cells (BMSCs) and osteocytes treated with TGFβ1. HLU mice showed reduced bone density, microstructural integrity, and dysregulated signaling (increased p-Smad2/3, decreased p-Smad1/5/8). BMP9 overexpression restored osteogenic differentiation in vitro and improved bone properties in vivo. However, RCCS failed to replicate osteogenic inhibition, likely due to shear stress. Despite challenges, BMP9 shows promise for treating disuse osteoporosis. Future research will refine vector specificity and reduce immunogenicity for clinical application.
由机械卸载引起的废用性骨质疏松与转化生长因子β（TGFβ）和骨形态发生蛋白（BMP）信号失调有关。本研究探讨了它们的作用，并评估了BMP9作为一种潜在治疗方法的效果。采用后肢卸载（HLU）小鼠模型来评估骨骼变化和信号改变。在体外，利用带有3D打印的旋转细胞培养系统（RCCS）模拟微重力环境。BMP9在经TGFβ1处理的骨髓间充质干细胞（BMSC）和骨细胞中过表达。HLU小鼠表现出骨密度降低、微观结构完整性受损以及信号失调（磷酸化Smad2/3增加，磷酸化Smad1/5/8减少）。BMP9过表达在体外恢复了成骨分化，并在体内改善了骨骼特性。然而，RCCS未能复制成骨抑制作用，这可能是由于剪切应力所致。尽管存在挑战，但BMP9在治疗废用性骨质疏松方面显示出前景。未来的研究将优化载体特异性并降低免疫原性，以用于临床应用。
