ArticleArthritis research & therapy2024
Development of primary osteoarthritis during aging in genetically diverse UM-HET3 mice.
Article in Arthritis research & therapy, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed.
- Micro-CT-based analysis of the murine osteochondral unit: a review and recommendations for standardized subchondral bone assessment.JBMR plus · 2026Review
- Targeting mitochondrial oxidative stress: A novel therapeutic strategy for degenerative joint diseases (Review).Biomedical reports · 2026Review
- Inbred C57BL/6J and C57BL/6N mice exhibit differential vascular dysfunction compared with outbred UM-HET3 mice.American journal of physiology. Heart and circulatory physiology · 2026Article
- Cerebrolysin Ameliorates Age-Induced Dendritic Spine Degeneration and Memory Decline in C57BL6 Mice.Neurochemical research · 2025Article
- Liver injury severity determines skeletal deterioration: a shared pathophysiological axis between MASLD and osteoarthritis.GeroScience · 2025Article
- Osteoarthritis as an evolutionary legacy: Biological ageing and chondrocyte hypertrophy.Osteoarthritis and cartilage open · 2025Review
- Targeting Cellular Senescence: Pathophysiology in Multisystem Age-Related Diseases.Biomedicines · 2025Review
- Characterization of craniofacial tissue aging in genetically diverse HET3 male mice with longevity treatment of 17-alpha estradiol.Archives of oral biology · 2025Article
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Abstract
backgroundPrimary osteoarthritis (OA) occurs without identifiable underlying causes such as previous injuries or specific medical conditions. Age is a major contributing factor to OA, and as one ages, various joint tissues undergo gradual change, including degeneration of the articular cartilage, alterations in subchondral bone (SCB) morphology, and inflammation of the synovium.
methodsWe investigated the prevalence of primary OA in aged, genetically diverse UM-HET3 mice. Articular cartilage (AC) integrity and SCB morphology were assessed in 182 knee joints of 22-25 months old mice using the Osteoarthritis Research Society International (OARSI) scoring system and micro-CT, respectively. Additionally, we explored the effects of methylene blue (MB) and mitoquinone (MitoQ), two agents that affect mitochondrial function, on the prevalence and progression of OA during aging.
resultsAged UM-HET3 mice showed a high prevalence of primary OA in both sexes. Significant positive correlations were found between cumulative AC (cAC) scores and synovitis in both sexes, and osteophyte formation in female mice. Ectopic chondrogenesis did not show significant correlations with cAC scores. Significant direct correlations were found between AC scores and inflammatory markers in chondrocytes, including matrix metalloproteinase-13, inducible nitric oxide synthase, and the NLR family pyrin domain containing-3 inflammasome in both sexes, indicating a link between OA severity and inflammation. Additionally, markers of cell cycle arrest, such as p16 and β-galactosidase, also correlated with AC scores. In male mice, no significant correlations were found between SCB morphology traits and cAC scores, while in female mice, significant correlations were found between cAC scores and tibial SCB plate bone mineral density. Notably, MB and MitoQ treatments influenced the disease's progression in a sex-specific manner. MB treatment significantly reduced cAC scores at the medial knee joint, while MitoQ treatment reduced cAC scores, but these did not reach significance.
conclusionsOur study provides comprehensive insights into the prevalence and progression of primary OA in aged UM-HET3 mice, highlighting the sex-specific effects of MB and MitoQ treatments. The correlations between AC scores and various pathological factors underscore the multifaceted nature of OA and its association with inflammation and subchondral bone changes.
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