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MIR155HG通过调节miR-155-5p和DKK1的表达来抑制骨髓间充质干细胞的成骨分化。

MIR155HG suppresses the osteogenic differentiation of bone marrow mesenchymal stem cells through regulating miR-155-5p and DKK1 expression.

作者信息

Li Weimin, Yang Cheng, Xu Jiamu, Ran Dongcheng, Wang Chunqing

机构信息

Department of Orthopedic, The Fourth People's Hospital of Guiyang, Guiyang Guizhou, 550002, China.

Department of Orthopedic, Guizhou Hospital of Beijing Jishuitan Hospital, Guiyang Guizhou, 550014, China.

出版信息

J Orthop Surg Res. 2025 Apr 19;20(1):392. doi: 10.1186/s13018-025-05798-w.

Abstract

BACKGROUND

Increasing evidence has demonstrated that non-coding RNAs, including the lncRNA MIR155HG, are involved in the pathogenesis of postmenopausal osteoporosis (PMOP). In the current study, we studied MIR155HG function in regulation of osteogenic differentiation and tried to reveal the underlying mechanisms.

METHODS

Forty blood samples taken from 20 PMOP patients (PMOP group) and 20 postmenopausal individuals without osteoporosis (control group) were used to compare the contents of MIR155HG and miR-155-5p via RT-PCR. Alizarin red S staining and ALP staining were used to evaluate the osteogenic differentiation potential of bone marrow mesenchymal stem cells (BMSCs).

RESULTS

Elevated levels of MIR155HG and miR-155-5p were observed in the blood samples of the PMOP group. Upregulation of MIR155HG resulted in decreased expression of OPN, OSX, ALP, RUNX2 and β-catenin but increased DKK1 expression, together with decreased Alizarin red S + and ALP + staining areas. However, downregulation of DKK1 did not obviously change the above indices induced by MIR155HG upregulation. Further experiments revealed that MIR155HG caused an increase in the expression of miR-155-5p, which also serves as an inhibitor of the osteogenic differentiation of BMSCs through binding to β-catenin. Consistent with DKK1 knockdown, downregulation of miR-155-5p only also did not obviously reverse the repressive effect of MIR155HG on osteoblastic differentiation, but downregulation of DKK1 and miR-155-5p synchronously restored the osteogenic differentiation ability of BMSCs suppressed by MIR155HG overexpression.

CONCLUSION

MIR155HG suppressed the osteoblastic differentiation of BMSCs by regulating miR-155-5p and DKK1 expression. Either inhibition of miR-155-5p and DKK1 or direct suppression of MIR155HG may be effective approaches for treating PMOP.

摘要

背景

越来越多的证据表明,包括lncRNA MIR155HG在内的非编码RNA参与了绝经后骨质疏松症(PMOP)的发病机制。在本研究中,我们研究了MIR155HG在调节成骨分化中的作用,并试图揭示其潜在机制。

方法

采集20例PMOP患者(PMOP组)和20例无骨质疏松症的绝经后个体(对照组)的40份血样,通过RT-PCR比较MIR155HG和miR-155-5p的含量。采用茜素红S染色和碱性磷酸酶(ALP)染色评估骨髓间充质干细胞(BMSC)的成骨分化潜能。

结果

PMOP组血样中MIR155HG和miR-155-5p水平升高。MIR155HG上调导致骨桥蛋白(OPN)、成骨特异性转录因子(OSX)、碱性磷酸酶(ALP)、核心结合因子α1(RUNX2)和β-连环蛋白表达降低,但 Dickkopf相关蛋白1(DKK1)表达增加,同时茜素红S阳性和ALP阳性染色面积减少。然而,DKK1下调并没有明显改变MIR155HG上调所诱导的上述指标。进一步实验表明,MIR155HG导致miR-155-5p表达增加,miR-155-5p也通过与β-连环蛋白结合而抑制BMSC的成骨分化。与DKK1敲低一致,miR-155-5p下调也没有明显逆转MIR155HG对成骨细胞分化的抑制作用,但DKK1和miR-155-5p同时下调可恢复被MIR155HG过表达抑制的BMSC的成骨分化能力。

结论

MIR155HG通过调节miR-155-5p和DKK1表达抑制BMSC的成骨分化。抑制miR-155-5p和DKK1或直接抑制MIR155HG可能是治疗PMOP的有效方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/368b/12008851/96933f930535/13018_2025_5798_Fig1_HTML.jpg

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