title: Annexin A2, up-regulated by IL-6, promotes the ossification of ligament fibroblasts from ankylosing spondylitis patients.
abstract: BACKGROUND
  Annexin A2, a calcium-dependent phospholipid binding protein, is involved in osteogenesis. The objective of the present study was to explore the expression of Annexin A2 in spinal ligament tissues (LT) of ankylosing spondylitis (AS) patients and determine its pathological functions.
  
  
  METHODS
  mRNA and protein expression of Annexin A2 was detected by real-time PCR and Western blotting, respectively. Interleukin-6 (IL-6) concentration in serum was assessed by enzyme linked immunosorbent assay. Alkaline phosphatase (ALP) activity was measured with ALP activity kit on a microplate reader.
  
  
  RESULTS
  mRNA and protein expression of Annexin A2 in LT, and IL-6 concentration in serum were significantly increased in AS patients. Moreover, exogenous IL-6 treatment significantly up-regulated Annexin A2 expression and ALP activity. Silencing of Annexin A2 expression significantly ameliorated IL-6-induced ossification of fibroblasts from AS patients, as indicated by ALP activity, expression of proteins associated with osteogenic differentiation, including bone morphogenetic protein-2, osteocalcin and osterix, and the ratio of osteoprotegerin to receptor activator of NF-κB ligand. Further MEK inhibitor experiments suggested that Annexin A2 may exert its function through extracellular signal-related kinase pathway.
  
  
  CONCLUSIONS
  Annexin A2, up-regulated by IL-6, may promote ligament ossification of AS patients.
authors.affiliation: Department of Orthopedics, The Eighty-eighth Military Hospital, Tai'an 271000, PR China.
authors.forename: Da-He
authors.initials: DH
authors.lastname: Li
authors.affiliation: Department of Orthopedics, Changhai Hospital Affiliated to the Second Military Medical University, Shanghai 200433, PR China.
authors.forename: Chong-Ru
authors.initials: CR
authors.lastname: He
authors.affiliation: Department of Ophthalmology, The Affiliated Hospital of Tai Shan Medical University, Tai'an 271000, PR China.
authors.forename: Fu-Ping
authors.initials: FP
authors.lastname: Liu
authors.affiliation: Department of Orthopedics, Changhai Hospital Affiliated to the Second Military Medical University, Shanghai 200433, PR China.
authors.forename: Jia
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Orthopedics, Jiangyan Traditional Chinese Medicine Hospital, Taizhou 225500, PR China.
authors.forename: Jin-Wei
authors.initials: JW
authors.lastname: Gao
authors.affiliation: Community Health Service Center of Yu Garden Street, Shanghai 200001, PR China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Orthopedics, Changhai Hospital Affiliated to the Second Military Medical University, Shanghai 200433, PR China. Electronic address: weidongxuch@sina.com.
authors.forename: Wei-Dong
authors.initials: WD
authors.lastname: Xu
mesh_terms: D017306:Annexin A2 / Q000096:biosynthesis*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D015850:Interleukin-6 / Q000097:blood / Q000494:pharmacology*; D008022:Ligaments / Q000187:drug effects / Q000378:metabolism*; D009999:Ossification, Heterotopic / Q000378:metabolism; D010012:Osteogenesis / Q000502:physiology*; D013167:Spondylitis, Ankylosing / Q000097:blood / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology
chemical_list: C472822:ANXA2 protein, human; D017306:Annexin A2; C508600:IL6 protein, human; D015850:Interleukin-6
keywords: Ankylosing spondylitis; Annexin A2; IL-6; Ossification