title: Altered microRNA expression profile in synovial fluid from patients with knee osteoarthritis with treatment of hyaluronic acid.
abstract: OBJECTIVE
  The aim of this study was to investigate the microRNA (miRNA) expression pattern in synovial fluid from patients with knee osteoarthritis (OA) after treatment with intra-articular injection of hyaluronan (HA).
  
  
  METHODS
  Twelve OA patients were enrolled in accordance with the Kellgren-Lawrence classification of knee OA. All patients received intra-articular injection of HA once a week for 5 weeks and were evaluated with the Western Ontario and McMaster Universities (WOMAC) index at baseline. TaqMan miRNA assay profiling was performed on synovial fluid RNAs extracted from OA patients pre-injection and after 5 weeks of treatment with HA. Validation was performed using independent samples, including ten healthy controls and ten matched OA patients.
  
  
  RESULTS
  Forty-three miRNAs (21 overexpressed miRNAs and 22 underexpressed miRNAs) were differentially expressed in OA patients before and after treatment with HA (P < 0.05, false discovery rate corrected). Further bioinformatics prediction by mirPath indicated that the differential miRNA signatures in synovial fluid extracted from the OA patients demonstrated primarily upregulation of the PI3K-Akt signaling pathway, mitogen-activated protein kinase signaling pathway, regulation of autophagy, mRNA surveillance pathway, and B cell receptor signaling pathway. In addition, TaqMan real-time reverse transcription polymerase chain reaction was performed for validation on miR-146a, miR-155, let-7a, miR-181a, miR-454, and let-7b, which were significantly changed in abundance, using an independent cohort of ten healthy controls and ten OA patients as compared with those with intra-articular injection of HA.
  
  
  CONCLUSIONS
  Our results demonstrated that dysregulation in miRNAs in synovial fluid from OA patients and their affected biologic cellular processes might play important role in OA pathogenesis and HA-mediated therapeutics.
authors.affiliation: Department of Orthopedics and Joint Surgery, Zhejiang Provincial People's Hospital, Hangzhou, 310014, People's Republic of China. xu_jifeng@hotmail.com.
authors.forename: Ji-Feng
authors.initials: JF
authors.lastname: Xu
authors.affiliation: Department of Orthopedics and Joint Surgery, Zhejiang Provincial People's Hospital, Hangzhou, 310014, People's Republic of China.
authors.forename: Shui-Jun
authors.initials: SJ
authors.lastname: Zhang
authors.affiliation: Department of Orthopedics and Joint Surgery, Zhejiang Provincial People's Hospital, Hangzhou, 310014, People's Republic of China.
authors.forename: Chen
authors.initials: C
authors.lastname: Zhao
authors.affiliation: Department of Orthopedics and Joint Surgery, Zhejiang Provincial People's Hospital, Hangzhou, 310014, People's Republic of China.
authors.forename: Bin-Song
authors.initials: BS
authors.lastname: Qiu
authors.affiliation: Department of Orthopedics and Joint Surgery, Zhejiang Provincial People's Hospital, Hangzhou, 310014, People's Republic of China.
authors.forename: Hai-Feng
authors.initials: HF
authors.lastname: Gu
authors.affiliation: Department of Orthopedics and Joint Surgery, Zhejiang Provincial People's Hospital, Hangzhou, 310014, People's Republic of China.
authors.forename: Jian-Fei
authors.initials: JF
authors.lastname: Hong
authors.affiliation: Department of Orthopedics and Joint Surgery, Zhejiang Provincial People's Hospital, Hangzhou, 310014, People's Republic of China.
authors.forename: Li
authors.initials: L
authors.lastname: Cao
authors.affiliation: Department of Orthopedics and Joint Surgery, Zhejiang Provincial People's Hospital, Hangzhou, 310014, People's Republic of China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Orthopedics and Joint Surgery, Zhejiang Provincial People's Hospital, Hangzhou, 310014, People's Republic of China.
authors.forename: Bing
authors.initials: B
authors.lastname: Xia
authors.affiliation: Department of Orthopedics and Joint Surgery, Zhejiang Provincial People's Hospital, Hangzhou, 310014, People's Republic of China.
authors.forename: Qin
authors.initials: Q
authors.lastname: Bi
authors.affiliation: Department of Cardiology, Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, 310009, People's Republic of China. wangypzju@163.com.
authors.forename: Ya-Ping
authors.initials: YP
authors.lastname: Wang
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage* / Q000627:therapeutic use; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015331:Cohort Studies; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D006820:Hyaluronic Acid / Q000008:administration & dosage* / Q000627:therapeutic use; D007270:Injections, Intra-Articular; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D020370:Osteoarthritis, Knee / Q000188:drug therapy* / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects; D013582:Synovial Fluid / Q000187:drug effects / Q000378:metabolism
chemical_list: D000276:Adjuvants, Immunologic; D035683:MicroRNAs; D006820:Hyaluronic Acid