Long non-coding RNA MEG3 regulates the progress of osteoarthritis by regulating the miR-34a/Klotho axis

Gaoxin Xiong; Shuangli Wang; Zhengjun Pan; Ning Liu; Donglei Zhao; Zhengang Zha; Rende Ning

doi:10.21037/atm-22-894

Long non-coding RNA MEG3 regulates the progress of osteoarthritis by regulating the miR-34a/Klotho axis

Ann Transl Med. 2022 Apr;10(8):454. doi: 10.21037/atm-22-894.

Authors

Gaoxin Xiong^{1

2}, Shuangli Wang^{1

2}, Zhengjun Pan², Ning Liu¹, Donglei Zhao², Zhengang Zha¹, Rende Ning²

Affiliations

¹ Department of Bone and Joint Surgery, Institute of Orthopedic Diseases, the First Affiliated Hospital of Jinan University, Jinan University, Guangzhou, China.
² Department of Joint Surgery, the First People's Hospital of Hefei City, Hefei, China.

Abstract

Background: Osteoarthritis (OA) is one of the most common chronic diseases today, and its prevalence and incidence are expected to increase as life expectancy increases. By investigating the inhibition of long non-coding RNA maternally expressed gene 3 (lncRNA MEG3) in OA, we hope to provide some new insights into the treatment of osteoarthritis.

Methods: By constructing an osteoarthritis model, the knee joint tissue of the model was observed using hematoxylin and eosin staining (HE) and computed tomography (CT). Detection of miR-34a and Klotho expression by fluorescent quantitative polymerase chain reaction (PCR) and Western blot. The lncRNA MEG3 overexpression vector was constructed and transfected into C28/I2 cells. Reverse transcription quantitative polymerase chain reaction (RT-qPCR) was used to detect the results of lncRNA MEG3 and miR-34a expression in each group of cells, and Western blot was used to detect the results of Klotho, recombinant fibroblast growth factor 23 (FGF23), B-cell lymphoma-2 (Bcl-2), BCL2-associated X (Bax), Transforming growth factor beta 1 (TGF-β1), cysteinyl aspartate specific proteinase 3 (Caspase3) and cysteinyl aspartate specific proteinase 8 (Caspase8) protein expression.

Results: Compared with the control group, HE and CT results showed significant pathological changes in the knee joint of the osteoarthritis model mice. and Klotho expression was significantly decreased and miR-34a expression was significantly increased in the model group (P<0.05). Compared with those in the control group, the expression levels of lncRNA MEG3, Klotho, FGF23, and Bcl-2 decreased significantly and the expression levels of microRNA-34a (miR-34a), Bax, TGF-β1, Caspase 3, and Caspase 8 increased sharply (P<0.05) in the lipopolysaccharides (LPS) group. Meanwhile, lncRNA MEG3 overexpression upregulated the expression of miR-34a, Bax, TGF-β1, Caspase3 and Caspase8, and downregulated the expression of Klotho, FGF23 and Bcl-2.

Conclusions: lncRNA MEG3 regulated the expression of FGF23, Bcl-2, Bax, TGF-β1, Caspase 3, and Caspase 8 by regulating the miR-34a/Klotho axis, thereby affecting the progress of OA.

Keywords: Klotho; Osteoarthritis (OA); cell apoptosis; lncRNA MEG3; miR-34a.