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Suppression of MALAT1 promotes human synovial mesenchymal stem cells enhance chondrogenic differentiation and prevent osteoarthritis of the knee in a rat model via regulating miR-212-5p/MyD88 axis

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Abstract

Osteoarthritis (OA) is one of the most common diseases of the skeleton. Long non-coding RNAs (lncRNAs) are emerging as key players in OA pathogenesis. This work sets out to determine the function of lncRNA MALAT1 in OA and the mechanisms by which it does so. Mesenchymal stem cells isolated from the human synovial membrane are called hSMSCs. The hSMSCs’ surface markers were studied using flow cytometry. To determine whether or not hSMSC might differentiate, researchers used a number of different culture settings and labeling techniques. The expression levels of associated genes and proteins were determined using quantitative real-time polymerase chain reaction (RT-qPCR), western blotting (WB), and immunostaining. A dual luciferase reporter experiment and RNA immunoprecipitation (RIP) test demonstrated the direct association between miR-212-5p and MALAT1 or MyD88. MALAT1 was downregulated during the chondrogenic differentiation of hSMSCs, and underexpression of MALAT1 promotes chondrogenesis in hSMSCs. Using dual luciferase reporter and RIP assays facilitated the identification of MALAT1 as a competitive endogenous RNA (ceRNA) that sequesters miR-212-5p. Additionally, the expression of MYD88 was regulated by MALAT1 through direct binding with miR-212-5p. Significantly, the effects of MALAT1 on the chondrogenic differentiation of hSMSCs were counteracted by miR-212-5p/MYD88. Furthermore, our in vivo investigation revealed that the inhibition of MALAT1 mitigated osteoarthritis progression in rat models. In conclusion, the promotion of chondrogenic differentiation in hSMSCs and the protective effect on cartilage tissue in OA can be achieved by suppressing MALAT1, which regulates the miR-212-5p/MyD88 axis.

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Acknowledgements

We would like to acknowledge the reviewers for their helpful comments on this paper.

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Authors and Affiliations

  1. Department of Rehabilitation Medicine, The Affiliated Hospital of Qingdao University, Qingdao, 266000, China

    Zhengyu Gao

  2. Department of Sports Medicine, The Affiliated Hospital of Qingdao University, Qingdao, 266000, China

    Cuicui Guo

  3. Department of Joint Surgery, The Affiliated Hospital of Qingdao University, Qingdao, 266003, China

    Shuai Xiang, Haining Zhang, Yingzhen Wang & Hao Xu

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  1. Zhengyu Gao
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  2. Cuicui Guo
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  3. Shuai Xiang
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  4. Haining Zhang
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  5. Yingzhen Wang
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  6. Hao Xu
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Contributions

BL and HX finished study design; HX and CD finished experimental studies; HX, CD, SX, and YW finished data analysis; HX finished manuscript editing. All authors read and approved the final manuscript.

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Correspondence to Hao Xu.

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The animal experiment was performed according to the National Institutes of Health Guide for Care and Use of Laboratory Animals and approved by the Affiliated Hospital of Qingdao University.

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The authors declare no competing interests.

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Gao, Z., Guo, C., Xiang, S. et al. Suppression of MALAT1 promotes human synovial mesenchymal stem cells enhance chondrogenic differentiation and prevent osteoarthritis of the knee in a rat model via regulating miR-212-5p/MyD88 axis. Cell Tissue Res 395, 251–260 (2024). https://doi.org/10.1007/s00441-024-03863-0

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  • DOI: https://doi.org/10.1007/s00441-024-03863-0

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