Inhibition of CC chemokine receptor 1 ameliorates osteoarthritis in mouse by activating PPAR-γ.

BACKGROUND: Osteoarthritis (OA) is a degenerative joint disease characterized by cartilage destruction and inflammation. CC chemokine receptor 1 (CCR1), a member of the chemokine family and its receptor family, plays a role in the autoimmune response. The impact of BX471, a specific small molecule inhibitor of CCR1, on CCR1 expression in cartilage and its effects on OA remain underexplored. METHODS: This study used immunohistochemistry (IHC) to assess CCR1 expression in IL-1ß-induced mouse chondrocytes and a medial meniscus mouse model of destabilization of the medial meniscus (DMM). Chondrocytes treated with varying concentrations of BX471 for 24 h were subjected to IL-1ß (10 ng/ml) treatment. The levels of the aging-related genes P16INK4a and P21CIP1 were analyzed via western blotting, and senescence-associated ß-galactosidase (SA-ß-gal) activity was measured. The expression levels of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), aggrecan (AGG), and the transcription factor SOX9 were determined through western blotting and RT‒qPCR. Collagen II, matrix metalloproteinase 13 (MMP13), and peroxisome proliferator-activated receptor (PPAR)-γ expression was analyzed via western blot, RT‒qPCR, and immunofluorescence. The impact of BX471 on inflammatory metabolism-related proteins under PPAR-γ inhibition conditions (using GW-9662) was examined through western blotting. The expression of MAPK signaling pathway-related molecules was assessed through western blotting. In vivo, various concentrations of BX471 or an equivalent medium were injected into DMM model joints. Cartilage destruction was evaluated through Safranin O/Fast green and hematoxylin-eosin (H&E) staining. RESULTS: This study revealed that inhibiting CCR1 mitigates IL-1ß-induced aging, downregulates the expression of iNOS, COX-2, and MMP13, and alleviates the IL-1ß-induced decrease in anabolic indices. Mechanistically, the MAPK signaling pathway and PPAR-γ may be involved in inhibiting the protective effect of CCR1 on chondrocytes. In vivo, BX471 protected cartilage in a DMM model. CONCLUSION: This study demonstrated the expression of CCR1 in chondrocytes. Inhibiting CCR1 reduced the inflammatory response, alleviated cartilage aging, and retarded degeneration through the MAPK signaling pathway and PPAR-γ, suggesting its potential therapeutic value for OA.

Association between ADAM12 Single-Nucleotide Polymorphisms and Knee Osteoarthritis: A Meta-Analysis.

OBJECTIVE: ADAM12 polymorphisms may be associated with the risk of knee osteoarthritis (KOA), but currently available evidence remains controversial. We performed this meta-analysis to confirm whether ADAM12 polymorphisms were associated with susceptibility of KOA. METHODS: A comprehensive literature search in PubMed, EMBASE, and ISI Web of Science was conducted to identify observational studies assessing the association between ADAM12 polymorphisms and susceptibility of KOA. The strength of association was indicated as odds ratio (OR) and the corresponding 95% confidence interval (95%CI). Four types of genetic model (additive model, dominant model, recessive model, and allele model) were evaluated for each included study. Subgroup analysis by ethnicity was performed. RESULTS: Seven case-control studies comprising a total of 3512 KOA patients and 5405 healthy controls were included in the meta-analysis. A significant association between rs1871054 and increased KOA risk was found in each genetic model. No significant association was found between KOA and rs3740199, rs1044122, or rs1278279 in any genetic model. CONCLUSION: Based on the findings of our study, there was a modest but statistically significant association between rs1871054 and risk of KOA in Asian population, while other polymorphisms (rs3740199, rs1044122, or rs1278279) in ADAM12 were not associated with KOA in any population.

[Characteristics of the sleep apnea syndrome in the aged].

OBJECTIVE: To study the characteristics of the sleep apnea syndrome in the aged. METHODS: Forty-two males who were suspicious of the sleep apnea syndrome (SAS) were detected with 7-hour polysomnography (PSG). RESULTS: The body mass index (BMI) and neck circumference showed no significant difference in the aged and middle aged groups. The apnea/hypopnea index (AHI) and microarousal index (MAI) were significantly lower, and the minimum oxygen saturation (SaO2) significantly higher in the aged than those in the middle aged (P < 0.05). Age was negatively correlated to AHI (r = -0.329, P < 0.05). The BMI and neck circumference were positively correlated to AHI (r = 0.326, P < 0.05; r = 0.306, P < 0.05, respectively). CONCLUSION: SAS patients are less severe in the aged excluding the affection of the BMI and neck circumference.