Circulating Osteoblast Precursors in Peripheral Blood Were Decreased after TNF-a 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 precursors in peripheral blood with 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 or disease modifying anti-rheumatic drugs. Peripheral blood mononuclear cells were collected and cultured in osteoblast growth medium. Once cell multilayering has been observed (about 7 days later), cells were moved to osteoblast differentiation medium and cultured for 3 weeks more. Then, cells were fixed and stained with alizarin S red to detect any calcified nodules. The optic density measurement of alizarin S red was performed to quantitative analysis. We evaluated the changes of 1) the number of circulating osteoblast precursors, 2) the optic density of alizarin S red staining of circulating osteoblast precursors, 3)the 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, Figure-2). The serum level of osteocalcin was increased after infliximab therapy (p = 0.01); but, that of CTX and RANKL was not changed sig