Hand osteoarthritis is a common heterogeneous joint disorder with unclear molecular mechanisms and no disease-modifying drugs.In this study,we performed single-cell RNA sequencing analysis to compare the cellular comp...Hand osteoarthritis is a common heterogeneous joint disorder with unclear molecular mechanisms and no disease-modifying drugs.In this study,we performed single-cell RNA sequencing analysis to compare the cellular composition and subpopulationspecific gene expression between cartilage with macroscopically confirmed osteoarthritis(n=5)and cartilage without osteoarthritis(n=5)from the interphalangeal joints of five donors.Of 105142 cells,we identified 13 subpopulations,including a novel subpopulation with inflammation-modulating potential annotated as inflammatory chondrocytes.Fibrocartilage chondrocytes exhibited extensive alteration of gene expression patterns in osteoarthritic cartilage compared with nonosteoarthritic cartilage.Both inflammatory chondrocytes and fibrocartilage chondrocytes showed a trend toward increased numbers in osteoarthritic cartilage.In these two subpopulations from osteoarthritic cartilage,the ferroptosis pathway was enriched,and expression of iron overload-related genes,e.g.,FTH1,was elevated.To verify these findings,we conducted a Mendelian randomization study using UK Biobank and a population-based cross-sectional study using data collected from Xiangya Osteoarthritis Study.Genetic predisposition toward higher expression of FTH1 mRNA significantly increased the risk of hand osteoarthritis(odds ratio=1.07,95%confidence interval:1.02–1.11)among participants(n=332668)in UK Biobank.High levels of serum ferritin(encoded by FTH1),a biomarker of body iron overload,were significantly associated with a high prevalence of hand osteoarthritis among participants(n=1241)of Xiangya Osteoarthritis Study(P-for-trend=0.037).In conclusion,our findings indicate that inflammatory and fibrocartilage chondrocytes are key subpopulations and that ferroptosis may be a key pathway in hand osteoarthritis,providing new insights into the pathophysiology and potential therapeutic targets of hand osteoarthritis.展开更多
AIM To investigate a comprehensive range of factors that contribute to long-term patient satisfaction post-total joint replacement(TJR)in people who had undergone knee or hip replacement for osteoarthritis.METHODS Par...AIM To investigate a comprehensive range of factors that contribute to long-term patient satisfaction post-total joint replacement(TJR)in people who had undergone knee or hip replacement for osteoarthritis.METHODS Participants(n=1151)were recruited from Nottinghamshire post-total hip or knee replacement.Questionnaire assessment included medication use,the pain-DETECT questionnaire(PDQ)to assess neuropathic pain-like symptoms(NP)and TJR satisfaction measured on average 4.8 years post-TJR.Individual factors were tested for an association with post-TJR satisfaction,before incorporating all factors into a full model.Data reduction was carried out using LASSO and receiveroperator characteristic(ROC)curve analysis was used to quantify the contribution of variables to post-TJR satisfaction.RESULTS After data reduction,the best fitting model for post-TJR satisfaction included various measures of pain,history of revision surgery,smoking,pre-surgical X-ray severity,WOMAC function scores and various comorbidities.ROC analysis of this model gave AUC=0.83(95%CI:0.80-0.85).PDQ scores were found to capture much of the variation in post-TJR satisfaction outcomes:AUC=0.79(0.75-0.82).Pre-surgical radiographic severity was associated with higher post-TJR satisfaction:OR_(satisfied)=2.06(95%CI:1.15-3.69),P=0.015.CONCLUSION These results highlight the importance of pre-surgical radiographic severity,post-TJR function,analgesic medication use and NP in terms of post-TJR satisfaction.The PDQ appears to be a useful tool in capturing factors that contribute to post-TJR satisfaction.展开更多
基金supported by the National Natural Science Foundation of China(81930071,82072502)the National Natural Science Foundation Regional Innovation and Development Joint Fund(U21A20352)+5 种基金the National Key Research and Development Project(2022YFC3601900,2022YFC2505500)the Project Program of National Clinical Research Center for Geriatric Disorders(Xiangya Hospital,2021LNJJ06,2022LNJJ07)the Natural Science Foundation of Hunan Province(2022JJ20100)the Key Research and Development Program of Hunan Province(2021SK2017)the Science and Technology Innovation Program of Hunan Province(2022RC3075)the Central South University Innovation-Driven Research Program(2023CXQD031)。
文摘Hand osteoarthritis is a common heterogeneous joint disorder with unclear molecular mechanisms and no disease-modifying drugs.In this study,we performed single-cell RNA sequencing analysis to compare the cellular composition and subpopulationspecific gene expression between cartilage with macroscopically confirmed osteoarthritis(n=5)and cartilage without osteoarthritis(n=5)from the interphalangeal joints of five donors.Of 105142 cells,we identified 13 subpopulations,including a novel subpopulation with inflammation-modulating potential annotated as inflammatory chondrocytes.Fibrocartilage chondrocytes exhibited extensive alteration of gene expression patterns in osteoarthritic cartilage compared with nonosteoarthritic cartilage.Both inflammatory chondrocytes and fibrocartilage chondrocytes showed a trend toward increased numbers in osteoarthritic cartilage.In these two subpopulations from osteoarthritic cartilage,the ferroptosis pathway was enriched,and expression of iron overload-related genes,e.g.,FTH1,was elevated.To verify these findings,we conducted a Mendelian randomization study using UK Biobank and a population-based cross-sectional study using data collected from Xiangya Osteoarthritis Study.Genetic predisposition toward higher expression of FTH1 mRNA significantly increased the risk of hand osteoarthritis(odds ratio=1.07,95%confidence interval:1.02–1.11)among participants(n=332668)in UK Biobank.High levels of serum ferritin(encoded by FTH1),a biomarker of body iron overload,were significantly associated with a high prevalence of hand osteoarthritis among participants(n=1241)of Xiangya Osteoarthritis Study(P-for-trend=0.037).In conclusion,our findings indicate that inflammatory and fibrocartilage chondrocytes are key subpopulations and that ferroptosis may be a key pathway in hand osteoarthritis,providing new insights into the pathophysiology and potential therapeutic targets of hand osteoarthritis.
基金Supported by PhD studentship awarded by the University of Nottingham(to Warner SC)EULAR project grant to AMV,No.108239ARUK Pain Centre,No.18769
文摘AIM To investigate a comprehensive range of factors that contribute to long-term patient satisfaction post-total joint replacement(TJR)in people who had undergone knee or hip replacement for osteoarthritis.METHODS Participants(n=1151)were recruited from Nottinghamshire post-total hip or knee replacement.Questionnaire assessment included medication use,the pain-DETECT questionnaire(PDQ)to assess neuropathic pain-like symptoms(NP)and TJR satisfaction measured on average 4.8 years post-TJR.Individual factors were tested for an association with post-TJR satisfaction,before incorporating all factors into a full model.Data reduction was carried out using LASSO and receiveroperator characteristic(ROC)curve analysis was used to quantify the contribution of variables to post-TJR satisfaction.RESULTS After data reduction,the best fitting model for post-TJR satisfaction included various measures of pain,history of revision surgery,smoking,pre-surgical X-ray severity,WOMAC function scores and various comorbidities.ROC analysis of this model gave AUC=0.83(95%CI:0.80-0.85).PDQ scores were found to capture much of the variation in post-TJR satisfaction outcomes:AUC=0.79(0.75-0.82).Pre-surgical radiographic severity was associated with higher post-TJR satisfaction:OR_(satisfied)=2.06(95%CI:1.15-3.69),P=0.015.CONCLUSION These results highlight the importance of pre-surgical radiographic severity,post-TJR function,analgesic medication use and NP in terms of post-TJR satisfaction.The PDQ appears to be a useful tool in capturing factors that contribute to post-TJR satisfaction.
