Zhou Wanlin, Huang Wenliang, Shen Xiongcheng, Huang Kun, Tian Renyuan, Yuan Ye, Deng Jiang
Department of Orthopedics, The Third Affiliated Hospital of Zunyi Medical University, Zunyi First People's Hospital, Zunyi, Guizhou Province, 563000, China.
Department of Orthopedics, Moutai Hospital, Renhuai, Guizhou Province, 564500, China.
Mol Biol Rep. 2025 Jun 6;52(1):559. doi: 10.1007/s11033-025-10648-3.
Osteoporosis is a prevalent metabolic bone disorder, especially in individuals with diabetes. Recent studies suggest that GLP-1 plays a positive role in regulating bone metabolism. However, the impact of GLP-1R on bone marrow-derived mesenchymal stem cells, particularly STRO-1-positive BMSCs, remains unclear. This study aims to investigate the impact of GLP-1R activation on the osteogenic differentiation potential of STRO-1-positive BMSCs.
BMSCs were isolated from the femurs and tibias of Sprague-Dawley rats, characterized by flow cytometry and immunofluorescence. The expression of osteogenic genes(COL-I, OCN, RUNX2) and osteoprotegerin(OPG) was assessed by qPCR and Western blot. Osteogenic differentiation was evaluated by alizarin red and alkaline phosphatase staining. The GLP-1R expression in STRO-1-positive and negative BMSCs was compared. Pharmacological interventions with GLP-1R agonists and antagonists were used to evaluate their effect on osteogenesis. The results show that STRO-1-positive BMSCs exhibited stronger osteogenic potential than STRO-1-negative BMSCs. GLP-1R activation enhanced osteogenesis, with the agonist group displaying the highest mineralization capacity despite showing lower osteogenic gene expression. The control group exhibited the highest gene expression but the weakest mineralization capacity. Furthermore, JNK/ERK mRNA and protein levels were reduced at varying degrees in the experimental groups.
STRO-1-positive BMSCs exhibit stronger osteogenic potential, which may be facilitated through GLP-1R activity at varying levels, promoting their differentiation into mature osteoblasts.
骨质疏松症是一种常见的代谢性骨病，在糖尿病患者中尤为常见。最近的研究表明，胰高血糖素样肽-1（GLP-1）在调节骨代谢中发挥积极作用。然而，GLP-1受体（GLP-1R）对骨髓间充质干细胞，特别是STRO-1阳性骨髓间充质干细胞的影响仍不清楚。本研究旨在探讨GLP-1R激活对STRO-1阳性骨髓间充质干细胞成骨分化潜能的影响。
从Sprague-Dawley大鼠的股骨和胫骨中分离出骨髓间充质干细胞，通过流式细胞术和免疫荧光进行鉴定。通过定量聚合酶链反应（qPCR）和蛋白质免疫印迹法评估成骨基因（I型胶原蛋白、骨钙素、RUNX2）和骨保护素（OPG）的表达。通过茜素红和碱性磷酸酶染色评估成骨分化。比较STRO-1阳性和阴性骨髓间充质干细胞中GLP-1R的表达。使用GLP-1R激动剂和拮抗剂进行药物干预，以评估它们对成骨作用的影响。结果显示，STRO-1阳性骨髓间充质干细胞比STRO-1阴性骨髓间充质干细胞表现出更强的成骨潜能。GLP-1R激活增强了成骨作用，激动剂组尽管成骨基因表达较低，但矿化能力最高。对照组基因表达最高，但矿化能力最弱。此外，实验组中JNK/ERK的信使核糖核酸（mRNA）和蛋白质水平不同程度降低。
STRO-1阳性骨髓间充质干细胞表现出更强的成骨潜能，这可能通过不同水平的GLP-1R活性促进其分化为成熟的成骨细胞。
