背景原发性骨关节炎(OA)的发生没有可识别的潜在原因,例如先前的损伤或特定的医学状况。年龄是OA的主要因素,随着年龄的增长,各种关节组织经历逐渐变化,包括关节软骨的退化,软骨下骨(SCB)形态的改变,滑膜发炎.方法调查老年人原发性OA的患病率,遗传多样性的UM-HET3小鼠。使用国际骨关节炎研究协会(OARSI)评分系统和micro-CT评估了22-25个月大的182只小鼠膝关节的关节软骨(AC)完整性和SCB形态,分别。此外,我们探索了亚甲基蓝(MB)和米托醌(MitoQ)的作用,两种影响线粒体功能的药物,关于老化过程中OA的患病率和进展。结果老年UM-HET3小鼠在两种性别中均显示出原发性OA的高患病率。在两种性别中,累积AC(cAC)得分与滑膜炎之间存在显着的正相关。和雌性小鼠的骨赘形成。异位软骨形成与cAC评分没有显着相关性。在软骨细胞中发现AC评分和炎症标志物之间存在显著的直接相关性,包括基质金属蛋白酶-13,诱导型一氧化氮合酶,和NLR家族pyrin结构域在两性中含有-3炎性体,表明OA严重程度和炎症之间的联系。此外,细胞周期停滞的标志,如p16和β-半乳糖苷酶,也与AC分数相关。在雄性小鼠中,SCB形态性状与CAC得分无显著相关性,而在雌性老鼠中,发现cAC评分与胫骨SCB板骨密度之间存在显着相关性。值得注意的是,MB和MitoQ治疗以性别特异性方式影响疾病的进展。MB治疗显著降低膝关节内侧cAC评分,而MitoQ治疗降低了cAC评分,但是这些没有达到意义。结论我们的研究为老年UM-HET3小鼠原发性OA的患病率和进展提供了全面的见解,强调MB和MitoQ治疗的性别特异性效应。AC评分与各种病理因素之间的相关性强调了OA的多面性及其与炎症和软骨下骨变化的关联。
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.