目的探究生长分化因子5(GDF5)rs143383基因多态性与膝关节骨性关节炎发生的相关性。方法检索建库至2022年1月1日已经发表的关于GDF5 rs143383基因多态性与膝关节骨性关节炎之间相关性的文献,检索数据库包括PubMed、Embase、Web of Science、中国知网、万方和维普数据库等。依据检索策略检索,16篇文献(17项数据)符合纳入排除标准,从所需研究中提取数据后,确定优势比(OR)及其95%置信区间(CI)以评估。通过漏斗图评估发表偏差。结果GDF5(rs143383)基因多态性与膝关节骨性关节炎发生之间具有明显相关性。在总体的等位基因模型(T vs C:OR=1.20,95%CI:1.14,1.26,P<0.01)、共显基因模型(TT vs CC:OR=1.45,95%CI:1.30,1.62,P<0.01)和显性基因模型(TT+TC vs CC:OR=1.29,95%CI:1.17,1.43,P<0.01),均提示GDF5基因多态性与膝关节骨性关节炎的发生有明显相关性。此外,我们还根据种族进行亚组分型,通过亚组分析在亚洲人群以及高加索人群的等位基因模型(亚洲人群:T vs C:OR=1.22,95%CI:1.13,1.30,P<0.01;高加索人群:T vs C:OR=1.18,95%CI:1.10,1.26,P<0.01)、共显基因模型(亚洲人群:TT vs CC:OR=1.58,95%CI:1.33,1.88,P<0.01;高加索人群:TT vs CC:OR=1.37,95%CI:1.19,1.59,P<0.01)和显性基因模型(亚洲人群:TT+TC vs CC:OR=1.40,95%CI:1.18,1.65,P<0.01;高加索人群:TT+TC vs CC:OR=1.24,95%CI:1.08,1.42,P<0.01)中均观察到了GDF5 rs143383基因多态性与膝关节骨性关节炎发生显著的关联,然而在非洲人群中无明显关联。结论GDF5 rs143383基因多态性与膝关节骨性关节炎发生具有显著联系,尤其在亚洲人群和高加索人群中具有相关性。
Objective:To construct a novel non-viral vector loaded with growth and differentiation factor-5(GDF-5) plasmid using chitosan,hyaluronic acid,and chondroitin sulfate for osteoarthritis (OA)gene therapy.Methods: Nano-microspheres (NMPs)were prepared by mixing chitosan,hyaluronic acid,and chondreitin sulfate.GDF-5 plasmid was encapsulated in the NMPs through electrostatic adsorption.The basic characteristics of the NMPs were observed,and then they were co-cultured with chondrocytes to observe their effects on extracellular matrix (ECM) protein expression.Finally,NMPs loaded with GDF-5were inje.cted into the articular cavities of rabbits to observe their therapeutic effects on OA in vivo.Results:NMPs exhibited good physicochemical properties and low cytotoxicity.Their average diameter was (0.61±0.20)μm,and encapsulation efficiency was (38.19±0.36)%.According to Cell Counting Kit-8(CCK-8)assay,relative cell viability was 75%-99%when the total weight of NMPs was less than 560μg. Transfection efficiency was (62.0±2.1)% in a liposome group,and (60.0±1.8)% in the NMP group.There was no sig- nificant difference between the two groups (P>0.05).Immunohistochemical staining results suggested that NMPs can successfully transfect chondrocytes and stimulate ECM protein expression in vitro.Compared with the control groups, the NMP group significantly promoted the expression of chondrocyte ECM in vivo (P<0.05),as shown by analysis of the biochemical composition of chondrocyte ECM.When NMPs were injected into OA model rabbits,the expression of ECM proteins in chondrocytes was significantly promoted and the progression of OA was slowed down.Conclusions: Based on these data,we think that these NMPs with excellent physicochemical and biological properties could be promising non-viral vectors for OA gene therapy.
