Adiponectin overexpression promotes fracture healing through regulating the osteogenesis and adipogenesis balance in osteoporotic mice

Adiponectin overexpression promotes fracture healing through regulating the osteogenesis and adipogenesis balance in osteoporotic mice
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DOI:
10.1007/s00774-023-01420-3
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发表时间:
2023-04
影响因子:
3.3
通讯作者:
Ju Zhang;Shibo Liu;Ze He;Hanghang Liu;Yao Liu;Pei Hu;Zhongming Li;Jiazhuang Xu;En Luo
Ju Zhang;Shibo Liu;Ze He;Hanghang Liu;Yao Liu;Pei Hu;Zhongming Li;Jiazhuang Xu;En Luo
中科院分区:
医学3区
文献类型:
--
作者:
Ju Zhang;Shibo Liu;Ze He;Hanghang Liu;Yao Liu;Pei Hu;Zhongming Li;Jiazhuang Xu;En Luo

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骨质疏松症总是表现为骨丢失,由脂肪组织替代;这很容易导致骨折,并伴有延迟和不良愈合。脂联素(APN)在骨髓间充质干细胞(BMSCs)中平衡成骨和成脂。因此,本研究探讨脂联素是否通过调节骨生成和脂肪生成之间的平衡来促进骨折愈合。材料和方法我们使用携带APN的腺病毒过表达载体(Ad-APN-GFP)治疗卵巢切除(OVX)小鼠BMSCs和骨质疏松性骨折,以研究APN在骨质疏松性骨折中骨微环境代谢中的作用。随后,我们建立了一个OVX小鼠和骨折模型,使用Ad-APN-GFP治疗,以探讨APN是否可以促进骨质疏松症小鼠骨折愈合。ResultsThe实验结果表明,APN是一个关键的分子在不同的分化方向在OVX小鼠BMSCs,具有促骨生成和抗脂肪生成的属性。重要的是,我们的研究表明,Ad-APN-GFP治疗促进骨生成和愈合周围的骨质疏松性骨折端。此外,我们确定,Sirt 1和Wnt信号密切相关的亲骨和抗脂肪生成承诺APN在OVX小鼠骨髓间充质干细胞和股骨tissues.ConclusionWe表明,APN过表达促进骨质疏松症骨折愈合。此外,APN过表达通过调节体外和体内成骨和脂肪生成之间的平衡来促进OVX小鼠BMSC和骨折端的骨形成。
IntroductionOsteoporosis invariably manifests as loss of bone, which is replaced by adipose tissue; this can easily lead to fractures, accompanied by delayed and poor healing. Adiponectin (APN) balances osteogenesis and adipogenesis in bone marrow mesenchymal stem cells (BMSCs). Therefore, this study explored whether adiponectin promotes bone fracture healing by regulating the balance between osteogenesis and adipogenesis.Materials and methodsWe used adenovirus overexpression vectors carrying APN (Ad-APN-GFP) to treat ovariectomized (OVX) mouse BMSCs and osteoporotic bone fractures to investigate the role of APN in bone microenvironment metabolism in osteoporotic fractures. We subsequently established an OVX mice and bone fracture model using Ad-APN-GFP treatment to investigate whether APN could promote bone fracture healing in osteoporotic mice.ResultsThe experimental results showed that APN is a critical molecule in diverse differentiation directions in OVX mouse BMSCs, with pro-osteogenesis and anti-adipogenesis properties. Importantly, our study revealed that Ad-APN-GFP treatment facilitates bone generation and healing around the osteoporotic fracture ends. Moreover, we identified that Sirt1 and Wnt signaling were closely related to the pro-osteogenesis and anti-adipogenesis commitment of APN in OVX mouse BMSCs and femoral tissues.ConclusionWe demonstrated that APN overexpression facilitates bone fracture healing in osteoporosis. Furthermore, APN overexpression promoted bone formation in OVX mouse BMSCs and bone fracture ends by regulating the balance between osteogenesis and adipogenesis both in vitro and in vivo.