title: The effect of anti-TNF treatment on osteoblastogenesis in ankylosing spondylitis: the number of circulating osteoblast-lineage cells in peripheral blood decreased after infliximab therapy in patients with ankylosing spondylitis.
abstract: OBJECTIVE
  The full effect of anti-TNF therapy on new bone formation is still in debate in spondylitis fields. We sought to obtain circulating osteoblast-lineage cells in peripheral blood from ankylosing spondylitis (AS) patients and healthy control subjects, and to evaluate the effect of before and after anti TNF-α therapy on osteoblastogenesis in patients with AS.
  
  
  METHODS
  Sixteen male patients with AS slated for infliximab therapy and 19 controls were recruited. We cultured osteoblast-lineage cells from peripheral blood and measured the optical density of their Alizarin red S staining. We also measured serum P1NP (procollagen type 1 N-terminal propeptide) as an early osteoblast differentiation marker, osteocalcin as a late osteoblast differentiation marker, and inflammatory markers.
  
  
  RESULTS
  There were significantly more circulating osteoblast-lineage cells in patients than in controls. The number of circulating osteoblast-lineage cells and optical density of Alizarin red S staining decreased 14 weeks after infliximab therapy (p=0.028); serum level of P1NP decreased, but that of osteocalcin increased (p=0.002 and 0.007, respectively).
  
  
  CONCLUSIONS
  Our data reveals that first, the circulating osteoblast-lineage cells are recoverable and increased in AS patients, and also that they decrease after infliximab therapy; second, infliximab therapy resolves early inflammation, but allows mature osteoblast differentiation in late inflammation. The culture of osteoblast-lineage cells in peripheral blood may be a candidate for a new modality with which to study spondylitis and other autoimmune diseases.
authors.affiliation: Rheumatism Centre, Department of Internal Medicine, School of Medicine, Inha University, Incheon, Republic of Korea.
authors.forename: Seong-Ryul
authors.initials: SR
authors.lastname: Kwon
authors.affiliation: Rheumatism Centre, Department of Internal Medicine, School of Medicine, Inha University, Incheon, Republic of Korea.
authors.forename: Kyong-Hee
authors.initials: KH
authors.lastname: Jung
authors.affiliation: Rheumatism Centre, Department of Internal Medicine, School of Medicine, Inha University, Incheon, Republic of Korea.
authors.forename: Mie-Jin
authors.initials: MJ
authors.lastname: Lim
authors.affiliation: Rheumatism Centre, Department of Internal Medicine, School of Medicine, Inha University, Incheon, Republic of Korea.
authors.forename: Min-Jung
authors.initials: MJ
authors.lastname: Son
authors.affiliation: Biomedical and Biological Sciences, School of Medicine, Inha University, Inha University, Incheon, Republic of Korea.
authors.forename: Byung Hyune
authors.initials: BH
authors.lastname: Choi
authors.affiliation: Occupational and Environmental Medicine, School of Medicine, Inha University, Incheon, Republic of Korea.
authors.forename: Shin-Goo
authors.initials: SG
authors.lastname: Park
authors.affiliation: Rheumatism Centre, Department of Internal Medicine, School of Medicine, Inha University, Incheon, Republic of Korea. parkwon@inha.ac.kr.
authors.forename: Won
authors.initials: W
authors.lastname: Park
mesh_terms: D000893:Anti-Inflammatory Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001688:Biological Products / Q000009:adverse effects / Q000627:therapeutic use*; D016022:Case-Control Studies; D002454:Cell Differentiation / Q000187:drug effects*; D019070:Cell Lineage; D002478:Cells, Cultured; D006801:Humans; D018836:Inflammation Mediators / Q000097:blood; D000069285:Infliximab / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D010006:Osteoblasts / Q000187:drug effects* / Q000473:pathology; D015675:Osteocalcin / Q000097:blood; D010012:Osteogenesis / Q000187:drug effects*; D010446:Peptide Fragments / Q000097:blood; D011347:Procollagen / Q000097:blood; D013167:Spondylitis, Ankylosing / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D013997:Time Factors; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000276:immunology
chemical_list: D000893:Anti-Inflammatory Agents; D001688:Biological Products; D018836:Inflammation Mediators; D010446:Peptide Fragments; D011347:Procollagen; C439524:TNF protein, human; D014409:Tumor Necrosis Factor-alpha; C047202:procollagen Type I N-terminal peptide; D015675:Osteocalcin; D000069285:Infliximab