山西中医药大学学报2026，Vol.27Issue(8)：885-897,13.DOI:10.19763/j.cnki.2096-7403.2026.05.10
m6A甲基转移酶METTL3、METTL14和WTAP在骨关节炎患者外周血单核细胞中的表达及临床意义
Expression and clinical significance of m6A methyltransferases METTL3,METTL14 and WTAP in peripheral blood mononuclear cells of patients with osteoarthritis
摘要
Abstract
Objective:To identify differentially expressed methyltransferases in peripheral blood mononuclear cells(PBMCs)of patients with osteoarthritis(OA),analyze their relationships with clinical indicators(inflammation,coagulation and lipid metabolism)and patient-reported outcomes,and provide new insights into the pathogenesis of OA and potential biomarkers.Methods:This study recruited 30 OA patients hospitalized in the Department of Rheumatology of The First Af-filiated Hospital of Anhui University of Chinese Medicine from October 2024 to January 2025,and 30 healthy controls from the physical examination center.Basic information and laboratory indicators(including inflammatory,coagulation and lipid metabolism parameters)of the 30 OA patients were collected using the Inpatient Data Processing System V1.0(2017SR422234).The patients had a mean age of 61.43±10.26 years,including 6 males(20.00%)and 24 females(80%),with a disease duration of 10.00(7.00,17.00)years.(1)Patients completed the Self-Perception of Patient(SPP)scale,in-cluding scores for cold-dampness syndrome(CDS),syndrome of damp-heat(SDH),syndrome of deficiency of spleen with surplus dampness(SDSSD),syndrome of blood stasis(SBS),Visual Analog Scale(VAS)score,Self-Rating Anxiety Scale(SAS)score,Self-Rating Depression Scale(SDS)score,and eight dimensions of the 36-Item Short Form Health Survey(SF-36):physical functioning(PF),role-physical(RP),bodily pain(BP),general health(GH),vitality(VT),social functioning(SF),role-emotional(RE),and mental health(MH).(2)The neutrophil-to-lymphocyte ratio(NLR),systemic inflammatory response index(SIRI)=neutrophil count×monocyte count/lymphocyte count,platelet-to-lymphocyte ratio(PLR),and sys-temic coagulation-inflammation index(SCI)=platelet count×fibrinogen/white blood cell count(PLT×FBG/WBC)were cal-culated.(3)Blood was collected and PBMCs were isolated,and total m6A levels in PBMCs were measured using a colorimet-ric method.(4)Five specimens were randomly selected from each group,and Western Blot was used to detect the protein expression levels of methyltransferases[methyltransferase-like protein 3(METTL3),methyltransferase-like protein 14(METTL14),Wilms tumor 1-associated protein(WTAP),RNA-binding motif protein 15B(RBM15B),vir-like m6A methyltransferase-associated protein(KIAA1429),Casitas B-lineage lymphoma translocation gene-like protein 1(CBLL1),METTL16,and zinc finger CCCH domain-containing protein 13(ZC3H13)].(5)Quantitative real-time PCR(RT-qPCR)was further used to detect the mRNA expression levels of the differentially expressed methyltransferases METTL3,METTL14 and WTAP in PBMCs of 30 OA patients and 30 healthy controls.(6)Correlations between the mRNA expression levels of METTL3,METTL14 and WTAP and patient age,sex,disease duration,various laboratory indicators,and SPP scale scores were analyzed.Results:(1)Total m6A levels in PBMCs of OA patients before treatment were significantly higher than those in healthy controls and the difference was statistically significant(P<0.01);after treatment,PBMC m6A levels decreased significantly compared with before treatment and the difference was statistically significant(P<0.01)and were not significantly different from those in healthy controls(P>0.05),indicating that changes in m6A levels were involved in the occurrence and development of OA.(2)Before treatment,the protein expression levels of METTL3,METTL14 and WTAP in PBMCs of OA patients were significantly higher than those in healthy controls and the difference was statistically significant(P<0.01);after treatment,they decreased significantly,with statistically significant differences compared with before treatment(P<0.01)and no significant differences compared with healthy controls(P>0.05).There were no statistically significant differences in the protein expression levels of RBM15B,KIAA1429,CBLL1,METTL16 and ZC3H13 in PBMCs of OA patients after treatment compared with before treatment or with healthy controls(P>0.05).These findings indicated that METTL3,METTL14,and WTAP might be key methyltransferases involved in the regulation of OA.(3)Correlation analysis showed that the mRNA ex-pression level of METTL3 in PBMCs of OA patients was negatively correlated with disease duration and positively correlated with lipid metabolism indicators[triglycerides(TG),total cholesterol(TC)and low-density lipoprotein cholesterol(LDL-C)].The mRNA expression level of METTL14 was positively correlated with inflammatory indicators[erythrocyte sedimentation rate(ESR),neutrophil count(NEU),white blood cell count(WBC)],coagulation indicators[fibrinogen(FBG),D-dimer(D-Dimer),platelet count(PLT)and SCI].The mRNA expression level of WTAP was positively correlated with ESR,FBG and D-Dimer and negatively correlated with PLR.Furthermore,both METTL14 and WTAP were negatively correlated with the VT and RE scores of the SF-36 and positively correlated with VAS,SAS,SDS and SBS TCM syndrome scores.These findings indicated that changes in METTL3,METTL14 and WTAP mRNA expression in PBMCs of OA patients after treatment were closely associated with improvements in the inflammatory-hypercoagulable state and SPP.Conclusion:The high expression of METTL3,METTL14 and WTAP in PBMCs of OA patients may participate in the occurrence and development of inflam-matory responses,hypercoagulable state and lipid metabolism disorders,as well as the deterioration of patient-reported out-comes during the disease course.This provides new insights into the pathogenesis of OA and potential biomarkers.关键词
骨关节炎/甲基转移酶/炎症反应/高凝状态/脂代谢Key words
OA/methyltransferases/inflammatory response/hypercoagulable state/lipid metabolism分类
医药卫生引用本文复制引用
贺明玉,刘健,孙艳秋,方妍妍,陈晓露,王帆帆..m6A甲基转移酶METTL3、METTL14和WTAP在骨关节炎患者外周血单核细胞中的表达及临床意义[J].山西中医药大学学报,2026,27(8):885-897,13.基金项目
安徽中医药大学产学研合作项目(2024HZ076) （2024HZ076）
安徽中医药大学2024年度临床科研项目(2024YFYLCZX15,2024YFYLCZX46) （2024YFYLCZX15,2024YFYLCZX46）
