PPARγ inhibition promotes osteogenic differentiation of bone marrow mesenchymal stem cells and fracture healing

IF 3 3区生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of cellular biochemistry Pub Date : 2024-04-15 DOI:10.1002/jcb.30568

Guohui Yang, Kexi Liu, Shengli Ma, Peiyi Qi

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Abstract

This study aimed to explore the effects of peroxisome proliferator-activated receptor γ (PPARγ) inhibition on fracture healing of nonunion and the underlying mechanisms. Bone marrow mesenchymal stem cells (BMSCs) were treated with PPARγ antagonist GW9662 (5 μM, 10 μM). Alkaline phosphatase (ALP) staining and Alizarin Red S was used to assess early stage of osteogenesis and osteogenic differentiation. GW9662 (1 mg/kg/day) were administered intraperitoneally into the rats with bone fracture. Bone healing processes in the rat femur fracture model were recorded and assessed by radiographic methods on Weeks 8, 14, and 20 postoperation. Osteogenesis and angiogenesis at the fracture sites were evaluated by radiographic and histological methods on postoperative Week 20. GW9662 treatment increased ALP activity and Alp mRNA expression in rat BMSCs. Moreover, GW9662 administration increased matrix mineralization and mRNA and protein levels of Bmp2 and Runx2 in the BMSCs. In addition, GW9662 treatment improved radiographic score in the fracture rats and increased osteogenesis-related proteins, including type I collagen, osteopontin, and osteoglycin, in the bone tissues of the fracture sites. In conclusion, PPARγ inhibition promotes osteogenic differentiation of rat BMSCs, as well as improves the fracture healing of rats through Bmp2/Runx2 signaling pathway in the rat model of bone fracture.

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抑制 PPARγ 可促进骨髓间充质干细胞的成骨分化和骨折愈合

本研究旨在探讨过氧化物酶体增殖激活受体γ（PPARγ）抑制剂对骨不连骨折愈合的影响及其内在机制。用 PPARγ 拮抗剂 GW9662（5 μM、10 μM）处理骨髓间充质干细胞（BMSCs）。碱性磷酸酶（ALP）染色和茜素红 S 用于评估成骨和成骨分化的早期阶段。给骨折大鼠腹腔注射 GW9662（1 毫克/千克/天）。大鼠股骨骨折模型的骨愈合过程在术后第 8、14 和 20 周通过放射学方法进行记录和评估。术后第 20 周，通过放射学和组织学方法对骨折部位的骨生成和血管生成进行评估。GW9662 治疗可提高大鼠 BMSCs 的 ALP 活性和 Alp mRNA 表达。此外，GW9662 还能增加基质矿化，提高 BMSCs 中 Bmp2 和 Runx2 的 mRNA 和蛋白水平。此外，GW9662 治疗还改善了骨折大鼠的放射学评分，并增加了骨折部位骨组织中的成骨相关蛋白，包括 I 型胶原、骨生成素和骨粘蛋白。总之，在大鼠骨折模型中，抑制 PPARγ 可促进大鼠 BMSCs 的成骨分化，并通过 Bmp2/Runx2 信号通路改善大鼠的骨折愈合。

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来源期刊

Journal of cellular biochemistry 生物-生化与分子生物学

CiteScore

9.90

自引率

0.00%

发文量

164

审稿时长

1 months

期刊介绍： The Journal of Cellular Biochemistry publishes descriptions of original research in which complex cellular, pathogenic, clinical, or animal model systems are studied by biochemical, molecular, genetic, epigenetic or quantitative ultrastructural approaches. Submission of papers reporting genomic, proteomic, bioinformatics and systems biology approaches to identify and characterize parameters of biological control in a cellular context are encouraged. The areas covered include, but are not restricted to, conditions, agents, regulatory networks, or differentiation states that influence structure, cell cycle & growth control, structure-function relationships.