Related Experiment Video
Updated: Dec 6, 2025
Software-Assisted Quantitative Measurement of Osteoarthritic Subchondral Bone Thickness
Published on: March 18, 2022
MicroRNA-34a-5p Promotes Joint Destruction During Osteoarthritis
Helal Endisha1, Poulami Datta2, Anirudh Sharma2
1Krembil Research Institute, University Health Network, and, University of Toronto, Toronto, Ontario, Canada.
Objective:
MicroRNA-34a-5p (miR-34a-5p) expression is elevated in the synovial fluid of patients with late-stage knee osteoarthritis (OA); however, its exact role and therapeutic potential in OA remain to be fully elucidated. This study was undertaken to examine the role of miR-34a-5p in OA pathogenesis.
Methods:
Expression of miR-34a-5p was determined in joint tissues and human plasma (n = 71). Experiments using miR-34a-5p mimic or antisense oligonucleotide (ASO) treatment were performed in human OA chondrocytes, fibroblast-like synoviocytes (FLS) (n = 7-9), and mouse OA models, including destabilization of the medial meniscus (DMM; n = 22) and the accelerated, more severe model of mice fed a high-fat diet and subjected to DMM (n = 11). Wild-type (WT) mice (n = 9) and miR-34a-knockout (KO) mice (n = 11) were subjected to DMM. Results were expressed as the mean ± SEM and analyzed by t-test or analysis of variance, with appropriate post hoc tests. P values less than 0.05 were considered significant. RNA sequencing was performed on WT and KO mouse chondrocytes.
Results:
Expression of miR-34a-5p was significantly increased in the plasma, cartilage, and synovium of patients with late-stage OA and in the cartilage and synovium of mice subjected to DMM. Plasma miR-34a-5p expression was significantly increased in obese patients with late-stage OA, and in the plasma and knee joints of mice fed a high-fat diet. In human OA chondrocytes and FLS, miR-34a-5p mimic increased key OA pathology markers, while miR-34a-5p ASO improved cellular gene expression. Intraarticular miR-34a-5p mimic injection induced an OA-like phenotype. Conversely, miR-34a-5p ASO injection imparted cartilage-protective effects in the DMM and high-fat diet/DMM models. The miR-34a-KO mice exhibited protection against DMM-induced cartilage damage. RNA sequencing of WT and KO chondrocytes revealed a putative miR-34a-5p signaling network.
Conclusion:
Our findings provide comprehensive evidence of the role and therapeutic potential of miR-34a-5p in OA.
Insights
MicroRNA-34a-5p (miR-34a-5p) is elevated in knee osteoarthritis (OA). Inhibiting miR-34a-5p shows therapeutic potential by protecting cartilage and reducing OA pathology in preclinical models.
Area of Science:
- Biochemistry
- Molecular Biology
- Immunology
Background:
- MicroRNA-34a-5p (miR-34a-5p) is upregulated in late-stage knee osteoarthritis (OA).
- The precise function and therapeutic utility of miR-34a-5p in OA pathogenesis are not fully understood.
Purpose of the Study:
- To investigate the role of miR-34a-5p in the development of knee osteoarthritis (OA).
- To evaluate the therapeutic potential of targeting miR-34a-5p for OA treatment.
Main Methods:
- miR-34a-5p expression analysis in human OA patient tissues and plasma.
- In vitro studies using human OA chondrocytes and fibroblast-like synoviocytes (FLS) treated with miR-34a-5p mimic or antisense oligonucleotide (ASO).
- In vivo studies using mouse OA models (DMM, high-fat diet/DMM) with intraarticular injections of miR-34a-5p mimic or ASO, and in miR-34a-knockout mice.
Main Results:
- miR-34a-5p expression was significantly increased in OA patient tissues and plasma, particularly in obese patients and in mouse models of OA.
- miR-34a-5p mimic exacerbated OA markers in vitro and induced OA-like phenotypes in vivo, while miR-34a-5p ASO demonstrated cartilage-protective effects.
- miR-34a-knockout mice showed protection against OA development in DMM models, and RNA sequencing identified a potential miR-34a-5p signaling network.
Conclusions:
- This study provides substantial evidence for the involvement of miR-34a-5p in OA pathogenesis.
- Targeting miR-34a-5p represents a promising therapeutic strategy for knee osteoarthritis.
Related Concept Videos
01:22MicroRNAs
01:22MicroRNAs
01:23Role of Matrix Metalloproteases in Degradation of ECM
01:24T Cell Types and Functions
Th1 cells stimulate dendritic cells to express necessary co-stimulatory molecules on their surfaces for...