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08.17 The paradoxical effects of tnf-α on osteoblastogenesis
  1. Seong-Ryul Kwon1,
  2. Won Park1,
  3. Kyong-Hee Jung1,
  4. Mie-Jin Lim1,
  5. Min-Jeong Son1,
  6. Byung-Heon Choi2,
  7. Shin-Goo Park3
  1. 1Rheumatism Centre, Department of Internal Medicine, School of Medicine, Inha University, Incheon, Republic of Korea
  2. 2Biomedical and Biological Sciences, School of Medicine, Inha University, Incheon, Republic of Korea
  3. 3Occupational and Environmental Medicine, School of Medicine, Inha University, Incheon, Republic of Korea

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 TNF-α on osteoblastogenesis in patients with AS before and after infliximab therapy.

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 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).

Conclusion Our data reveals first, TNF-α stimulates osteoblastogenesis before infliximab therapy in patients with AS; 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 study spondylitis and other autoimmune diseases.

Funding This study is supported by grant from the National Research Foundation of Korea (NRF-2014R1A1A2058007) to Dr. S-R Kwon

Keywords
  • inflammation
  • ankylosing spondylitis
  • osteoblasts
  • infliximab

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