Characterization of miR-335-5p and miR-335-3p in human osteoarthritic tissues

Arthritis Research & Therapy

Research

Navdeep Kaur¹  Madhu Baghel¹  Thomas G. Wilson¹  Shabana Amanda Ali²  Vasilios Moutzouros³  Jason Davis³ 

[1] Bone and Joint Center, Henry Ford Health, 6135 Woodward Avenue, 48202, Detroit, MI, USA;Department of Orthopedic Surgery, Henry Ford Health, Detroit, MI, USA;Bone and Joint Center, Henry Ford Health, 6135 Woodward Avenue, 48202, Detroit, MI, USA;Department of Orthopedic Surgery, Henry Ford Health, Detroit, MI, USA;Department of Physiology, Michigan State University, East Lansing, MI, USA;Center for Molecular Medicine and Genetics, Wayne State University, Detroit, MI, USA;Department of Orthopedic Surgery, Henry Ford Health, Detroit, MI, USA;

关键词: Osteoarthritis;    MicroRNAs;    Human tissues;    Knee;    Hip;   

DOI  :  10.1186/s13075-023-03088-6

 received in 2023-03-31, accepted in 2023-06-06,  发布年份 2023

来源: Springer

【 摘 要 】

ObjectiveWe aimed to characterize the expression patterns, gene targets, and functional effects of miR-335-5p and miR-335-3p among seven primary human knee and hip osteoarthritic tissue types.MethodsWe collected synovial fluid, subchondral bone, articular cartilage, synovium, meniscus/labrum, infrapatellar/acetabular fat, anterior cruciate ligament/ligamentum teres, and vastus medialis oblique/quadratus femoris muscle (n = 7–20) from surgical patients with early- or late-stage osteoarthritis (OA) and quantified miR-335-5p and miR-335-3p expression by real-time PCR. Predicted gene targets were measured in knee OA infrapatellar fat following miRNA inhibitor transfection (n = 3), and prioritized gene targets were validated following miRNA inhibitor and mimic transfection (n = 6). Following pathway analyses, we performed Oil-Red-O staining to assess changes in total lipid content in infrapatellar fat.ResultsShowing a 227-fold increase in knee OA infrapatellar fat (the highest expressing tissue) versus meniscus (the lowest expressing tissue), miR-335-5p was more abundant than miR-335-3p (92-fold increase). MiR-335-5p showed higher expression across knee tissues versus hip tissues, and in late-stage versus early-stage knee OA fat. Exploring candidate genes, VCAM1 and MMP13 were identified as putative direct targets of miR-335-5p and miR-335-3p, respectively, showing downregulation with miRNA mimic transfection. Exploring candidate pathways, predicted miR-335-5p gene targets were enriched in a canonical adipogenesis network (p = 2.1e − 5). Modulation of miR-335-5p in late-stage knee OA fat showed an inverse relationship to total lipid content.ConclusionOur data suggest both miR-335-5p and miR-335-3p regulate gene targets in late-stage knee OA infrapatellar fat, though miR-335-5p appears to be more prominent, with tissue-, joint-, and stage-specific effects.

【 授权许可】

CC BY   
© The Author(s) 2023

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