Document Type
Article
Publication Date
6-8-2024
Original Citation
Poudel S,
Ruff R,
Yildirim G,
Miller R,
Harrison D,
Strong R,
Kirsch T,
Yakar S.
Development of primary osteoarthritis during aging in genetically diverse UM-HET3 mice. Arthritis Res Ther. 2024;26(1):118. Epub 20240608.
Keywords
JMG, Animals, Male, Female, Mice, Aging, Osteoarthritis, Cartilage, Articular, Methylene Blue, Ubiquinone, Disease Models, Animal, Disease Progression
JAX Source
Arthritis Res Ther. 2024;26(1):118. Epub 20240608.
ISSN
1478-6362
PMID
38851726
DOI
https://doi.org/10.1186/s13075-024-03349-y
Grant
This work was also supported by the National Institutes of Health grant to The Jackson Laboratory Nathan Shock Center of Excellence in the Basic Biology of Aging AG038070, U01-AG022303 to RAM, UO1-AG022308 to DEH,
Abstract
BACKGROUND: Primary 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.
METHODS: We 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.
RESULTS: Aged 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.
CONCLUSIONS: Our 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.
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.