title: Increasing expression of substance P and calcitonin gene-related peptide in synovial tissue and fluid contribute to the progress of arthritis in developmental dysplasia of the hip.
abstract: BACKGROUND
  Developmental dysplasia of the hip (DDH) is a common musculoskeletal disorder that has pain and loss of joint function as major pathological features. In the present study, we explored the mechanisms of possible involvement and regulation of substance P (SP) and calcitonin gene-related peptide (CGRP) in the pathological and inflammatory processes of arthritis in DDH.
  
  
  METHODS
  Blood, synovial tissue and fluid samples were collected from patients diagnosed with different severities of DDH and from patients with femoral neck fracture. Levels of SP, CGRP and inflammatory cytokines in synovium and synovial fluid (SF) in the different groups were evaluated by immunohistochemistry, real-time PCR and enzyme-linked immunosorbent assay (ELISA). Correlations between neuropeptides and inflammatory cytokines in SF were evaluated by partial correlation analysis. The proinflammatory effects of SP and CGRP on synoviocytes obtained from patients with moderate DDH were investigated in vitro by real-time PCR and ELISA. The mechanisms of those effects were evaluated by Western blot analysis and nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) DNA binding assay.
  
  
  RESULTS
  Significantly increased levels of neuropeptides and inflammatory cytokines were observed in synovium and SF from patients in the severe DDH group compared with the moderate DDH and control groups. In moderate DDH samples, SP in SF correlated with tumor necrosis factor (TNF)-α, and CGRP in SF correlated with TNF-α and interleukin (IL)-10. In the severe DDH group, SP in SF correlated with interleukin (IL)-1β, TNF-α and IL-10. CGRP in SF correlated with TNF-α. Additionally, SP might have had obvious proinflammatory effects on synoviocytes through the activation of NF-κB.
  
  
  CONCLUSIONS
  The upregulation of SP and CGRP in synovium and SF might participate in the inflammatory process of arthritis in DDH. The activation of the NF-κB pathway seems indispensable in the proinflammatory effect of SP on synoviocytes. This original discovery may indicate a potential clinical drug target and the development of innovative therapies for DDH.
authors.affiliation: Department of Orthopaedic Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, No. 1665, Kongjiang Road, Yangpu District, Shanghai, 200092, People's Republic of China. wanghuigk@163.com.
authors.forename: Hui
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Orthopaedic Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, No. 1665, Kongjiang Road, Yangpu District, Shanghai, 200092, People's Republic of China. blue_nicky@hotmail.com.
authors.forename: Xiang
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Orthopaedic Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, No. 1665, Kongjiang Road, Yangpu District, Shanghai, 200092, People's Republic of China. bone_man@163.com.
authors.forename: Ji-Ye
authors.initials: JY
authors.lastname: He
authors.affiliation: Department of Orthopaedic Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, No. 1665, Kongjiang Road, Yangpu District, Shanghai, 200092, People's Republic of China. zxf272@126.com.
authors.forename: Xin-Feng
authors.initials: XF
authors.lastname: Zheng
authors.affiliation: Department of Orthopaedic Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, No. 1665, Kongjiang Road, Yangpu District, Shanghai, 200092, People's Republic of China. lide_doctor@163.com.
authors.forename: De
authors.initials: D
authors.lastname: Li
authors.affiliation: Department of Orthopaedic Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, No. 1665, Kongjiang Road, Yangpu District, Shanghai, 200092, People's Republic of China. lizheng_haha@sina.com.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Li
authors.affiliation: Department of Orthopaedic Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, No. 1665, Kongjiang Road, Yangpu District, Shanghai, 200092, People's Republic of China. zhujf2002@163.com.
authors.forename: Jun-Feng
authors.initials: JF
authors.lastname: Zhu
authors.affiliation: Department of Orthopaedic Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, No. 1665, Kongjiang Road, Yangpu District, Shanghai, 200092, People's Republic of China. samsonov@126.com.
authors.forename: Chao
authors.initials: C
authors.lastname: Shen
authors.affiliation: Department of Orthopaedic Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, No. 1665, Kongjiang Road, Yangpu District, Shanghai, 200092, People's Republic of China. caiguiquan99@sina.com.
authors.forename: Gui-Quan
authors.initials: GQ
authors.lastname: Cai
authors.affiliation: Department of Orthopaedic Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, No. 1665, Kongjiang Road, Yangpu District, Shanghai, 200092, People's Republic of China. chenxdmd@163.com.
authors.forename: Xiao-Dong
authors.initials: XD
authors.lastname: Chen
mesh_terms: D000328:Adult; D001168:Arthritis / Q000175:diagnosis / Q000453:epidemiology / Q000378:metabolism*; D015740:Calcitonin Gene-Related Peptide / Q000096:biosynthesis*; D018450:Disease Progression; D005260:Female; D005786:Gene Expression Regulation; D006618:Hip Dislocation, Congenital / Q000175:diagnosis / Q000453:epidemiology / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D013373:Substance P / Q000096:biosynthesis*; D013582:Synovial Fluid / Q000378:metabolism*; D013583:Synovial Membrane / Q000378:metabolism / Q000473:pathology; D055815:Young Adult
chemical_list: D013373:Substance P; D015740:Calcitonin Gene-Related Peptide