Vaspin deficiency failed to promote the proliferation of BMSCs in osteoarthritis

Vaspin deficiency failed to promote the proliferation of BMSCs in osteoarthritis
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Vaspin 缺乏未能促进骨关节炎中 BMSC 的增殖

DOI:
10.1111/1756-185x.14010
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发表时间:
2020-10-27
影响因子:
2.5
通讯作者:
Guan, Zhenpeng
Guan, Zhenpeng
中科院分区:
医学4区
文献类型:
--
作者:
Wang, Junfeng;Chen, Zhongqiang;Guan, Zhenpeng

文献摘要

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目的探讨血管素在骨关节炎(OA)骨髓微环境中对骨间充质干细胞(BMSCs)增殖的影响及其分子机制。方法本研究包括15例非肥胖的老年严重膝关节OA患者和15例非肥胖的股骨颈骨折对照。所有患者都接受了髋关节或膝关节置换术以恢复关节形状和功能。术中取骨髓标本,酶联免疫吸附法测定vaspin和转化生长因子(TGF)- β 1水平,细胞计数试剂盒-8观察vaspin对骨髓间充质干细胞增殖的影响。实时聚合酶链反应和western blot检测vaspin对参与PI3K/ Akt信号通路的Akt基因和蛋白的影响。结果OA患者骨髓血管蛋白水平明显低于对照组(P = 0.03)。此外,我们发现骨髓中vaspin和tgf - β 1浓度之间存在显著相关性(r = 0.60, P < 0.01)。此外,体外实验表明,当vaspin处理浓度为150 ng/mL时,BMSCs的增殖明显促进(P < 0.01)。同时,我们发现vaspin处理后BMSCs中Akt信使RNA和pAkt蛋白水平升高(P < 0.05)。结论本研究结果提示OA骨髓微环境中存在vaspin的异常表达,vaspin可能通过促进PI3K/AKT信号通路的激活来调节骨髓间充质干细胞的增殖。
Objective The aim of this study was to estimate the possible role of vaspin in the proliferation of bone mesenchymal stem cells (BMSCs) and its molecular mechanisms in the bone marrow microenvironment of osteoarthritis (OA).Methods This study included 15 non-obese elderly patients with severe knee OA and 15 non-obese controls with femoral neck fracture. Patients all underwent hip or knee arthroplasty surgery to restore joint shape and function. Bone marrow samples were taken during surgery to estimate vaspin and transforming growth factor (TGF)-beta 1 levels by enzyme-linked immunosorbent assay and to observe the effect of vaspin on BMSCs proliferation by Cell Counting Kit-8. Real-time polymerase chain reaction and western blot were performed to evaluate the effect of vaspin on the genes and proteins of Akt involved in the PI3K/AKT signaling pathway.Results Bone marrow vaspin levels were significantly lower in OA patients compared to controls (P = .03). Furthermore, we found a significant correlation between vaspin and TGF-beta 1 concentrations in bone marrow (r = .60, P < .01). In addition, the in vitro studies indicated the proliferation of BMSCs was significantly promoted when the vaspin treatment concentration was 150 ng/mL (P < .01). Meanwhile, we found that the Akt messenger RNA and pAkt protein levels in BMSCs were increased after vaspin treatment (P < .05).Conclusion The findings of this study suggest there was abnormal expression of vaspin in OA bone marrow microenvironment, and vaspin likely had a mediator role in the proliferation of BMSCs, which may work by promoting the activation of the PI3K/AKT signaling pathway.