Circulating Osteoblasts in Peripheral Blood Were Decresed after TNF-α Blocker Therapy in Patients with Ankylosing Spondylitis

초록

Background The relationship between inflammation and new bone formation is unsolved question in area of spondylitis. First hypothesis is that inflammation is the process that sets in motion the chain of events that leads to ankylosis; an opposite one has proposed that an unknown pathogenic trigger simultaneously induces both inflammation and activation of new bone formation. Objective We investigated the circulating osteoblast in peripheral blood with novel cell culture technique before and 14 weeks after infliximab therapy in patients with ankylosing spondylitis. Methods Male Fifteen individuals with ankylosing spondylitis were enrolled. They met the modified New York criteria and the candidates of infliximab therapy, refractory to non-steroidal anti-inflammatory drugs. Peripheral blood mononuclear cells were collected and cultured in growth medium. Once cell multilayering has been observed (about 7 days), cells were moved to differentiation medium and cultured for 3 weeks. Then, cells were fixed and stained with alizarin S stain to detect any calcified nodules. The optic density measurement of alizarin S was performed to quantitative analysis. We evaluated 1) the change of numbers of circulating osteoblast precursors, 2) the optic density of alizarin S red staining of circulating osteoblast precursors, 3) osteocalcin, c-terminal telopeptide (CTX-1), receptor activator of NFkB ligand (RANKL) with enzyme linked immunosorbent assay (ELISA) in peripheral blood before and after 14 week infliximab therapy in patients with ankylosing spondylitis. Results The number of osteoblast precursor cells (Figure-1) and optic density of alizarin S were decreased after infliximab therapy (p = 0.018 for optic density of alizarin S). The serum level of osteocalcin was increased after infliximab therapy (p = 0.01); but, CTX and RANKL was not changed significantly. Conclusion The circulating osteoblasts in peripheral blood were decreased significantly after 14 weeks of infli