Tohoku J. Exp. Med., 2025 May, 266(3)

Long Non-Coding RNA RASSF8-AS1 Promotes M1 Macrophage Polarization in Osteoarthritis via Moderating miR-27a-3p

Haijun Shi,¹ Meizhi Liu,² Wenhan Ma,³ Zhigang Chen⁴ and Yongyun Shi⁵

¹The First People’s Hospital of Aksu Prefecture, Xinjiang, China
²Department of Rheumatology, Hebei General Hospital, Shijiazhuang, Hebei, China
³Department of Cardiology, the Second Hospital of Shandong University, Jinan, Shandong, China
⁴Department of Orthopedic Surgery, The First Affiliated Hospital of Xi’an Medical University, Xi’an, Shaanxi, China
⁵Department of 1st Orthopedic Surgery, Nanjing Luhe People’s Hospital, Nanjing, Jiangsu, China

Long non-coding RNAs are major regulators in the pathophysiology of osteoarthritis (OA), which involves the dysfunction of cartilage and synovium. The aim of this study was, therefore, to discover the role of RASSF8-AS1 in cartilage degradation and M1 macrophage polarization during OA. Healthy and OA cartilage and synovium were collected. After measuring RASSF8-AS1 levels in tissues and lipopolysaccharide (LPS)- or IL-1β-induced cells, the role of RASSF8-AS1 in the expression of cartilage degradation markers and M1 macrophage molecules was assessed in vitro. The apoptotic rate of IL-1β-stimulated chondrocytes, with or without RASSF8-AS1 overexpression, was quantified using flow cytometry. RASSF8-AS1 was significantly upregulated not only in cartilage and synovium from OA patients, but also in IL-1β- or LPS-induced cells, compared to normal controls. A decrease in RASSF8-AS1 level increased the expression of chondrogenic markers, but reduced the expression of genes encoding matrix-degrading proteases, thereby reducing cell apoptosis. Downregulation of RASSF8-AS1 reduced the M1 macrophage markers in RAW264.7 cells and bone marrow-derived macrophages. RASSF8-AS1 may be a ceRNA for miR-27a-3p. These findings support the role of RASSF8-AS1 as a promoting factor of cartilage degradation and M1 macrophage polarization in OA.

Key words —— macrophages; miR-27a-3p; osteoarthritis; RASSF8-AS1

© 2025 Tohoku University Medical Press

===============================

Tohoku J. Exp. Med., 2025 May, 266(3), 219-227.

Correspondence: Yongyun Shi, Department of 1st Orthopedic Surgery, Nanjing Luhe People’s Hospital, No. 9, Jiankang Lane, Xiongzhou Town, Luhe District, Nanjing, Jiangsu 211500, China.

e-mail: SHIyongyun_lhry@163.com

Correspondence: Zhigang Chen, Department of Orthopedic Surgery, The First Affiliated Hospital of Xi’an Medical University, No. 48, Fenghao West Road, Lianhu District, Xi’an, Shaanxi 710000, China.

e-mail: czki7u@163.com