title: Involvement of Notch1/Hes signaling pathway in ankylosing spondylitis.
abstract: We aimed to investigate the role of Notch1/Hes signaling pathway in the pathogenesis of abnormal ossification of hip ligament in patients with ankylosing spondylitis (AS). 22 AS patients scheduled for artificial hip arthroplasty were randomly chosen as AS group. As controls, we used 4 patients diagnosed with transcervical fracture who underwent hip replacement surgery. Notch1 and Hes mRNA expressions were detected by real-time fluorescent quantitative polymerase chain reaction (RFQ-PCR). Immunohistochemistry (IHC) was used to detect Notch1 and Hes protein expression. Correlation analyses of Notch-l and Hes with AS-related clinical factors were conducted with spearman's correlation analysis and partial correlation analysis. RFQ-PCR results showed significant differences in Notch1 and Hes mRNA expressions between AS group and the control group (all P<0.05). IHC analysis further indicated positive nuclear signals of Notch1 and Hes protein, indicating functional activation of the Notch1 and Hes pathways. Semi-quantitative IHC showed a higher Notch1 and Hes expression levels in AS group compared to the control group (all P<0.05). Correlation analysis suggested that Hes protein expression was positively associated with the clinical course of the disease in AS patients. In conclusion, Notch1 and Hes overexpression was clearly detected in hip joint ligaments of AS patients, Hes protein expression was associated with the clinical course of AS. Taken together, we suggest that signaling pathways mediated by Notch1-Hes may contribute to ligament ossification of hip joints in AS patients.
authors.affiliation: Department of Orthopedic Surgery, Tongren Hospital Affiliated to Shanghai Jiaotong University School of Medicine Shanghai 200336, P.R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Xu
authors.affiliation: Department of Orthopedic Surgery, Tongren Hospital Affiliated to Shanghai Jiaotong University School of Medicine Shanghai 200336, P.R. China.
authors.forename: Chao-Ge
authors.initials: CG
authors.lastname: Liang
authors.affiliation: Department of Orthopedic Surgery, Tongren Hospital Affiliated to Shanghai Jiaotong University School of Medicine Shanghai 200336, P.R. China.
authors.forename: Yi-Fan
authors.initials: YF
authors.lastname: Li
authors.affiliation: Department of Orthopedic Surgery, Tongren Hospital Affiliated to Shanghai Jiaotong University School of Medicine Shanghai 200336, P.R. China.
authors.forename: Yun-Han
authors.initials: YH
authors.lastname: Ji
authors.affiliation: Department of Orthopedic Surgery, Tongren Hospital Affiliated to Shanghai Jiaotong University School of Medicine Shanghai 200336, P.R. China.
authors.forename: Wen-Jun
authors.initials: WJ
authors.lastname: Qiu
authors.affiliation: Department of Orthopedic Surgery, Tongren Hospital Affiliated to Shanghai Jiaotong University School of Medicine Shanghai 200336, P.R. China.
authors.forename: Xian-Zhong
authors.initials: XZ
authors.lastname: Tang
mesh_terms: D000328:Adult; D051792:Basic Helix-Loop-Helix Proteins / Q000032:analysis* / Q000235:genetics; D016022:Case-Control Studies; D005260:Female; D006621:Hip Joint / Q000737:chemistry* / Q000473:pathology; D018398:Homeodomain Proteins / Q000032:analysis* / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D008023:Ligaments, Articular / Q000737:chemistry* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009999:Ossification, Heterotopic; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D051881:Receptor, Notch1 / Q000032:analysis* / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D013167:Spondylitis, Ankylosing / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism*
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D018398:Homeodomain Proteins; D012333:RNA, Messenger; D051881:Receptor, Notch1; C497761:NOTCH1 protein, human
keywords: Notch1; ankylosing spondylitis; clinical course; hairy enhancer of split; hip joint ligament; mRNA expressions; protein expressions; signaling pathway