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Standardized Histomorphometric Evaluation of Osteoarthritis in a Surgical Mouse Model
Published on: May 6, 2020
Mouse microRNA signatures in joint ageing and post-traumatic osteoarthritis
Catarina I G D Castanheira1, James R Anderson1, Yongxiang Fang2
1Musculoskeletal and Ageing Science, Institute of Life Course and Medical Sciences, University of Liverpool, Liverpool, L7 8TX, UK.
Objective:
This study investigated mice serum and joint microRNA expression profiles in ageing and osteoarthritis to elucidate the role of microRNAs in the development and progression of disease, and provide biomarkers for ageing and osteoarthritis.
Design:
Whole joints and serum samples were collected from C57BL6/J male mice and subjected to small RNA sequencing. Groups used included; surgically-induced post-traumatic osteoarthritis, (DMM; 24 months-old); sham surgery (24 months-old); old mice (18 months-old); and young mice (8 months-old). Differentially expressed microRNAs between the four groups were identified and validated using real-time quantitative PCR. MicroRNA differential expression data was used for target prediction and pathway analysis.
Results:
In joint tissues, miR-140-5p, miR-205-5p, miR-682, miR-208b-3p, miR-499-5p, miR-455-3p and miR-6238 were differentially expressed between young and old groups; miR-146a-5p, miR-3474, miR-615-3p and miR-151-5p were differentially expressed between DMM and Sham groups; and miR-652-3p, miR-23b-3p, miR-708-5p, miR-5099, miR-23a-3p, miR-214-3p, miR-6238 and miR-148-3p between the old and DMM groups. The number of differentially expressed microRNAs in serum was higher, some in common with joint tissues including miR-140-5p and miR-455-3p between young and old groups; and miR-23b-3p, miR-5099 and miR-6238 between old and DMM groups.We confirmed miR-140-5p, miR-499-5p and miR-455-3p expression to be decreased in old mouse joints compared to young, suggesting their potential use as biomarkers of joint ageing in mice.
Conclusions:
MiR-140-5p, miR-499-5p and miR-455-3p could be used as joint ageing biomarkers in mice. Further research into these specific molecules in human tissues is now warranted to check their potential suitability as human biomarkers of ageing.
Insights
MicroRNAs miR-140-5p, miR-499-5p, and miR-455-3p show decreased expression in aging mouse joints. These microRNAs may serve as potential biomarkers for joint aging in mice.
Area of Science:
- Molecular Biology
- Biochemistry
- Genomics
Background:
- MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression.
- Dysregulation of miRNA expression is implicated in various diseases, including osteoarthritis.
- Understanding miRNA profiles in aging and osteoarthritis is crucial for developing diagnostic and therapeutic strategies.
Purpose of the Study:
- To investigate serum and joint microRNA expression profiles in aging and osteoarthritis in mice.
- To elucidate the role of miRNAs in the development and progression of osteoarthritis.
- To identify potential biomarkers for aging and osteoarthritis.
Main Methods:
- Small RNA sequencing of whole joint and serum samples from C57BL6/J male mice.
- Comparison of miRNA expression across four groups: young (8 months), old (18 months), sham surgery (24 months), and surgically-induced post-traumatic osteoarthritis (DMM, 24 months).
- Validation of differentially expressed miRNAs using real-time quantitative PCR and pathway analysis.
Main Results:
- Several miRNAs were differentially expressed in joint tissues and serum between the studied groups.
- Specific miRNAs, including miR-140-5p, miR-499-5p, and miR-455-3p, showed decreased expression in old mouse joints compared to young mice.
- Serum miRNA profiles showed a higher number of differentially expressed miRNAs, with some overlapping with joint tissue findings.
Conclusions:
- MiR-140-5p, miR-499-5p, and miR-455-3p show potential as biomarkers for joint aging in mice.
- Further investigation in human tissues is warranted to assess their suitability as human aging biomarkers.

