Hu Menglong, Wu Likun, Wei Erfan, Pan Xingtong, Zhu Qiyue, Xiuyun Xv, Lv Letian, Dong Xinyi, Liu Hao, Liu Yunsong
Department of Prosthodontics, Peking University School and Hospital of StomatologyPeking University School and Hospital of Stomatology, Beijing, 100081, China.
National Center of Stomatology, National Clinical Research Center for Oral Diseases, National Engineering Research Center of Oral Biomaterials and Digital Medical Devices, Beijing Key Laboratory of Digital Stomatology, Research Center of Engineering and Technology for Computerized Dentistry Ministry of Health, NMPA Key Laboratory for Dental Materials, Beijing, 100081, China.
Stem Cell Res Ther. 2025 Apr 23;16(1):201. doi: 10.1186/s13287-025-04320-7.
Osteoporosis, a common bone disorder, is primarily managed pharmacologically. However, existing medications are associated with non-trivial side-effects. Sildenafil, which already finds many clinical applications, promotes angiogenesis and cellular differentiation. Osteoporotic patients often exhibit a reduced intraosseous vasculature and impaired cellular differentiation; sildenafil may thus usefully treat osteoporosis.
Here, the effects of sildenafil on the osteogenic differentiation of human mesenchymal stem cells (hMSCs) were explored, as were the molecular mechanisms in play. We treated hMSCs with varying concentrations of sildenafil and measured cell proliferation and osteogenic differentiation in vitro. We used a mouse model of subcutaneous ectopic osteogenesis to assess sildenafil's effect on hMSC osteogenic differentiation in vivo. We also explored the effects of sildenafil on bone loss in tail-suspended (TS) and ovariectomized (OVX) mice. Mechanistically, we employed RNA-sequencing to define potentially relevant molecular pathways.
The appropriate concentrations of sildenafil significantly enhanced osteogenic hMSC differentiation; the optimal sildenafil concentration may be 10 mg/L. Sildenafil mitigated osteoporosis in OVX and TS mice. The appropriate concentrations of sildenafil probably promoted hMSC osteogenic differentiation by acting on the transforming growth factor-β (TGF-β) signaling pathway.
In conclusion, sildenafil enhanced hMSC osteogenic differentiation and inhibited bone loss. Sildenafil may usefully treat osteoporosis. Our findings offer new insights into the physiological effects of the medicine.
骨质疏松症是一种常见的骨骼疾病，主要通过药物治疗。然而，现有药物存在明显的副作用。已在许多临床应用中使用的西地那非可促进血管生成和细胞分化。骨质疏松症患者常表现出骨内血管系统减少和细胞分化受损；因此，西地那非可能对治疗骨质疏松症有效。
在此，我们探讨了西地那非对人间充质干细胞（hMSC）成骨分化的影响及其相关分子机制。我们用不同浓度的西地那非处理hMSC，并在体外测量细胞增殖和成骨分化。我们使用皮下异位成骨小鼠模型评估西地那非在体内对hMSC成骨分化的影响。我们还研究了西地那非对尾部悬吊（TS）和去卵巢（OVX）小鼠骨质流失的影响。从机制上讲，我们采用RNA测序来确定潜在的相关分子途径。
适当浓度的西地那非显著增强了hMSC的成骨分化；最佳西地那非浓度可能为10mg/L。西地那非减轻了OVX和TS小鼠的骨质疏松症。适当浓度的西地那非可能通过作用于转化生长因子-β（TGF-β）信号通路促进hMSC的成骨分化。
总之，西地那非增强了hMSC的成骨分化并抑制了骨质流失。西地那非可能对治疗骨质疏松症有效。我们的研究结果为该药物的生理作用提供了新的见解。
