PMID- 38168298
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20240122
DP  - 2024 Jan 14
TI  - Development of primary osteoarthritis during aging in genetically diverse UM-HET3 
      mice.
LID - 2023.12.16.571693 [pii]
LID - 10.1101/2023.12.16.571693 [doi]
AB  - This study investigated the prevalence and progression of primary osteoarthritis 
      (OA) in aged UM-HET3 mice. Using the Osteoarthritis Research Society 
      International (OARSI) scoring system, we assessed articular cartilage (AC) 
      integrity in 182 knee joints of 22-25 months old mice. 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 (MMP-13), inducible nitric oxide synthase (iNOS), and 
      the NLR family pyrin domain containing-3 (NLRP3) inflammasome in both sexes, 
      indicating a link between OA severity and inflammation. Additionally, markers of 
      cell cycle arrest, such as p16 and beta-galactosidase, also correlated with AC 
      scores. Using micro-CT, we examined the correlations between subchondral bone 
      (SCB) morphology traits and 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. Finally, 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. 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. In conclusion, 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.
FAU - Poudel, Sher Bahadur
AU  - Poudel SB
AUID- ORCID: 0000-0003-3733-4648
FAU - Ruff, Ryan R
AU  - Ruff RR
FAU - Yildirim, Gozde
AU  - Yildirim G
FAU - Miller, Richard A
AU  - Miller RA
FAU - Harrison, David E
AU  - Harrison DE
FAU - Strong, Randy
AU  - Strong R
FAU - Kirsch, Thorsten
AU  - Kirsch T
FAU - Yakar, Shoshana
AU  - Yakar S
LA  - eng
PT  - Preprint
DEP - 20240114
PL  - United States
TA  - bioRxiv
JT  - bioRxiv : the preprint server for biology
JID - 101680187
PMC - PMC10760163
EDAT- 2024/01/04 01:18
MHDA- 2024/01/04 01:19
PMCR- 2024/01/19
CRDT- 2024/01/03 10:39
PHST- 2024/01/04 01:18 [pubmed]
PHST- 2024/01/04 01:19 [medline]
PHST- 2024/01/03 10:39 [entrez]
PHST- 2024/01/19 00:00 [pmc-release]
AID - 2023.12.16.571693 [pii]
AID - 10.1101/2023.12.16.571693 [doi]
PST - epublish
SO  - bioRxiv [Preprint]. 2024 Jan 14:2023.12.16.571693. doi: 
      10.1101/2023.12.16.571693.