Circulating miR-126-3p is a mechanistic biomarker for knee osteoarthritis

Thomas G. Wilson, Madhu Baghel, Navdeep Kaur, Indrani Datta, Ian Loveless, Pratibha Potla, Devin Mendez, Logan Hansen, Kevin Baker, T. Sean Lynch, Vasilios Moutzouros, Jason Davis and Shabana Amanda Ali ()
Additional contact information
Thomas G. Wilson: Henry Ford Health + Michigan State University Health Sciences
Madhu Baghel: Henry Ford Health + Michigan State University Health Sciences
Navdeep Kaur: Henry Ford Health + Michigan State University Health Sciences
Indrani Datta: Henry Ford Health + Michigan State University Health Sciences
Ian Loveless: Henry Ford Health + Michigan State University Health Sciences
Pratibha Potla: University Health Network
Devin Mendez: Henry Ford Health + Michigan State University Health Sciences
Logan Hansen: Henry Ford Health
Kevin Baker: Henry Ford Health + Michigan State University Health Sciences
T. Sean Lynch: Henry Ford Health
Vasilios Moutzouros: Henry Ford Health
Jason Davis: Henry Ford Health
Shabana Amanda Ali: Henry Ford Health + Michigan State University Health Sciences

Nature Communications, 2025, vol. 16, issue 1, 1-13

Abstract: Abstract Osteoarthritis is a major contributor to pain and disability worldwide, yet there are currently no validated soluble biomarkers or disease-modifying treatments. Given that microRNAs are promising mechanistic biomarkers that can be therapeutically targeted, in this study, we aimed to identify and prioritize reproducible circulating microRNAs associated with radiographic knee osteoarthritis. Across four independent cohorts, we find circulating miR-126-3p is elevated in knee osteoarthritis versus controls. Across six primary human knee osteoarthritis tissues, miR-126-3p is highest in subchondral bone, fat pad and synovium, and lowest in cartilage. Following both intravenous and intra-articular miR-126-3p mimic treatment in a surgical mouse model of knee osteoarthritis, we show reduced disease severity in males. In human knee osteoarthritis biospecimens, miR-126-3p mimic treatment reduces genes and markers associated with angiogenesis, as well as genes linked to osteogenesis, adipogenesis, and synovitis—processes secondary to angiogenesis. Our findings indicate that miR-126-3p is elevated in knee osteoarthritis and mitigates disease severity, supporting its potential as a biomarker and therapeutic target.

Date: 2025
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DOI: 10.1038/s41467-025-57308-5

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