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

Clin Exp Rheumatol. 2017 Sep-Oct;35(5):837-843. Epub 2017 Mar 31.

Abstract

Objectives: 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.

MeSH terms

  • Anti-Inflammatory Agents / adverse effects
  • Anti-Inflammatory Agents / therapeutic use*
  • Biological Products / adverse effects
  • Biological Products / therapeutic use*
  • Case-Control Studies
  • Cell Differentiation / drug effects*
  • Cell Lineage*
  • Cells, Cultured
  • Humans
  • Inflammation Mediators / blood
  • Infliximab / adverse effects
  • Infliximab / therapeutic use*
  • Male
  • Osteoblasts / drug effects*
  • Osteoblasts / pathology
  • Osteocalcin / blood
  • Osteogenesis / drug effects*
  • Peptide Fragments / blood
  • Procollagen / blood
  • Spondylitis, Ankylosing / drug therapy*
  • Spondylitis, Ankylosing / immunology
  • Spondylitis, Ankylosing / pathology
  • Time Factors
  • Treatment Outcome
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors*
  • Tumor Necrosis Factor-alpha / immunology

Substances

  • Anti-Inflammatory Agents
  • Biological Products
  • Inflammation Mediators
  • Peptide Fragments
  • Procollagen
  • TNF protein, human
  • Tumor Necrosis Factor-alpha
  • procollagen Type I N-terminal peptide
  • Osteocalcin
  • Infliximab