Zhiduo Li, Weijun Zhang

Department of Orthopaedics, Xuzhou No.1 People’s Hospital, the Affiliated Xuzhou Municipal Hospital of Xuzhou Medical University, Xuzhou, China

Keywords: Chondrocytes, LINC00472, miR-361-5p, MECP2, osteoarthritis.

Abstract

Objectives: This study aimed to investigate the effect of LINC00472 in osteoarthritis (OA) and its molecular mechanism.

Patients and methods: This prospective study was conducted with 110 patients (59 females, 51 males; mean age: 58.6±10.3 years; range, 37 to 79 year) with OA and 101 healthy controls (58 females, 43 males; mean age: 60.6±10.3 years; range, 35 to 78 years) between June 2020 and November 2022. First, we measured LINC00472 levels in OA patients using RT-qPCR (real-time quantitative reverse transcription polymerase chain reaction). Afterward, we treated human chondrocytes with interleukin (IL)-1β, which aimed to construct an OA cellular model to explore the function of LINC00472 in OA. Messenger RNA levels were detected by RT-qPCR. Apoptosis was measured by flow cytometry. Cell viability was measured by CCK-8 (cell counting kit-8) assay. Enzyme-linked immunosorbent assay was used to detect inflammatory factor levels. Finally, we verified the targeting of miR-361-5p with LINC00472 and MECP2 by luciferase assay and RNA immunoprecipitation.

Results: In OA patients and OA cells, LINC00472 and MECP2 levels were increased, and miR-361-5p levels were decreased. LINC00472 levels were negatively correlated with miR-361-5p levels and positively correlated with MECP2 levels. In human chondrocytes, LINC00472 knockdown inhibited apoptosis, cellular inflammation, and extracellular matrix degradation. However, miR-361-5p inhibitor reversed these effects. In addition, LINC00472 knockdown downregulated MECP2 levels, and miR-361-5p inhibitor reversed the effect.

Conclusion: LINC00472 is involved in chondrocyte apoptosis, extracellular matrix degradation, and cellular inflammation in OA through the miR-361-5p/MECP2 axis. LINC00472 may regulate OA development by increasing MECP2 expression through sponged miR-361-5p and may be a new target for OA diagnosis and treatment.

Citation: Li Z, Zhang W. Analysis of LINC00472 as a biomarker of osteoarthritis and its clinical value. Arch Rheumatol 2024;39(4):529-540. doi: 10.46497/ArchRheumatol.2024.10739.

Author Contributions

Conceptualization, data curation, formal analysis, investigation, methodology, Z.L., W.Z.; Resources, software, validation, visualization, writing-original draft, Z.L.; Project administration, supervision, visualization, writing-review & editing: W.Z.

Conflict of Interest

The authors declared no conflicts of interest with respect to the authorship and/or publication of this article.

Financial Disclosure

This work was funded by Xuzhou Medical University Science and Technology Park “Innovation and Entrepreneurship Program” (General Program), project number CXCYYB2024014.

Data Sharing Statement

The data that support the findings of this study are available from the corresponding author upon reasonable request.