<br>Wnt10b 通过 Wnt/β-catenin 信号通路调节骨质疏松症中脂肪干细胞的成骨,Cell Proliferation

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Wnt10b 通过 Wnt/β-catenin 信号通路调节骨质疏松症中脂肪干细胞的成骨
Cell Proliferation ( IF 5.9 ) Pub Date : 2023-06-20 , DOI: 10.1111/cpr.13522
Kui Huang _{1,

2} , Shuyu Cai _{2,

3} , Ting Fu ₃ , Qiang Zhu _{1,

2} , Lin Liu _{1,

2} , Zhihao Yao ₁ , Pengcheng Rao ₁ , Xiaorong Lan ₂ , Qing Li ₂ , Jingang Xiao _{1,

2,

3,

4}

Affiliation

我们之前的研究结果表明，成骨能力受损的骨质疏松脂肪干细胞（OP-ASC）的Wnt10b RNA 表达显着低于 ASC。目前尚不清楚 OP-ASC 的成骨潜力受损与Wnt10b表达之间的关系。本研究旨在阐明Wnt10b在 OP-ASC 中的潜在分子机制和功能作用，并研究其在逆转 OP-ASC 受损的成骨分化潜力方面的潜在应用。 OP-ASC 和 ASC 是从双侧卵巢切除 (OVX) 的骨质疏松 (OP) 小鼠和正常小鼠的腹股沟脂肪中收获的。 qPCR和WB用于检测OP-ASC和ASC中Wnt10b RNA表达的不同水平。对OP-ASCs采用慢病毒介导的Wnt10b表达调控，并通过qPCR和WB体外实验检测Wnt信号通路中关键分子和关键成骨因子的表达水平。使用茜素红染色测定 OP-ASC 的成骨能力。最后，通过显微计算机断层扫描、苏木精和伊红染色、Masson三色染色和免疫组织化学扫描并检测掺有改良OP-ASC的BCP支架对OP小鼠颅骨临界缺损（CSCD）的修复效果。首先，我们发现 OP-ASC 中Wnt10b的 RNA 和蛋白表达水平均显着低于 ASC。体外实验中，上调Wnt10b可以激活Wnt信号通路，增加β-catenin、Lef1、Runx2和骨桥蛋白（Opn）的表达，从而增强OP-ASC的成骨能力。此外，过表达Wnt10b的OP-ASC可以促进骨质疏松小鼠CSCD的修复，增加体内新骨体积、骨矿物质密度以及新骨中Opn表达的增加。综上所述，在体外和体内实验中， Wnt10b的过表达可以部分促进OP-ASC向成骨分化，并通过激活Wnt/β-catenin信号通路加速骨缺损的愈合。该研究证实了Wnt10b在调节OP-ASCs成骨分化能力中的重要作用，并表明Wnt10b可能成为逆转OP-ASCs受损的成骨能力以治疗OP患者骨缺损的潜在治疗靶点。

"点击查看英文标题和摘要"

Wnt10b regulates osteogenesis of adipose-derived stem cells through Wnt/β-catenin signalling pathway in osteoporosis

Our previous finding revealed that the Wnt10b RNA expression of osteoporotic adipose-derived stem cells (OP-ASCs) with impaired osteogenic capacity was significantly reduced than that of ASCs. There are no ideas that the relationship between the OP-ASCs' impaired osteogenic potential and Wnt10b expression. This study aimed to indicate the potential molecular mechanisms and functional role of Wnt10b in OP-ASCs, as well as to investigate a potential application to reverse the OP-ASCs' impaired osteogenic differentiation potential. The OP-ASCs and ASCs were harvested from the inguinal fat of osteoporosis (OP) mice with bilateral ovariectomy (OVX) and normal mice. qPCR and WB were used to detect the different levels of the expression of the Wnt10b RNA in both OP-ASCs and ASCs. Lentiviral-mediated regulation of Wnt10b expression was employed for OP-ASCs, and the detection of the expression levels of key molecules in the Wnt signalling pathway and key osteogenic factors was performed through qPCR and WB in vitro experiments. The capacity of OP-ASCs to osteogenesis was determined using alizarin red staining. Lastly, the repair effect of the BCP scaffolds incorporating modified OP-ASCs on the critical-sized calvarial defects (CSCDs) in OP mice was scanned and detected by micro-computed tomography, haematoxylin and eosin staining, Masson's trichrome staining and immunohistochemistry. First, we discovered that both the RNA and protein expression levels of Wnt10b were significantly lower in OP-ASCs than that in ASCs. In vitro experiments, upregulation of Wnt10b could activate the Wnt signalling pathway, and increase expression of β-catenin, Lef1, Runx2 and osteopontin (Opn), thereby enhancing the osteogenic ability of OP-ASCs. In addition, the OP-ASCs with Wnt10b-overexpressing could promote the repair of CSCD in osteoporotic mice with increasing new bone volume, bone mineral density, and increased expression of Opn in new bone in vivo. Taken together, overexpression of Wnt10b could partially facilitate the differentiation of OP-ASCs towards osteogenesis and accelerated the healing of bone defects by activating the Wnt/β-catenin signalling pathway in vitro and in vivo experiments. This study confirmed the important role of Wnt10b in regulating the osteogenic differentiation capability of OP-ASCs and indicated Wnt10b could be a potential therapeutic target for reversing the impaired osteogenic capabilities of OP-ASCs to therapy bone defects of OP patients.

更新日期：2023-06-20

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