Kwon Seong-Ryul, Jung Kyong-Hee, Lim Mie-Jin, Son Min-Jung, Choi Byung Hyune, Park Shin-Goo, Park Won
Rheumatism Centre, Department of Internal Medicine, School of Medicine, Inha University, Incheon, Republic of Korea.
Biomedical and Biological Sciences, School of Medicine, Inha University, Inha University, Incheon, Republic of Korea.
Clin Exp Rheumatol. 2017 Sep-Oct;35(5):837-843. Epub 2017 Mar 31.
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.
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.
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).
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.
在脊柱关节炎领域,抗TNF治疗对新骨形成的全面影响仍存在争议。我们试图从强直性脊柱炎(AS)患者和健康对照者的外周血中获取循环成骨细胞系细胞,并评估抗TNF-α治疗前后对AS患者成骨细胞生成的影响。
招募了16名计划接受英夫利昔单抗治疗的男性AS患者和19名对照者。我们从外周血中培养成骨细胞系细胞,并测量其茜素红S染色的光密度。我们还测量了血清I型前胶原N端前肽(P1NP)作为早期成骨细胞分化标志物、骨钙素作为晚期成骨细胞分化标志物以及炎症标志物。
患者循环成骨细胞系细胞显著多于对照者。英夫利昔单抗治疗14周后,循环成骨细胞系细胞数量和茜素红S染色光密度降低(p = 0.028);血清P1NP水平降低,但骨钙素水平升高(分别为p = 0.002和0.007)。
我们的数据表明,首先,AS患者循环成骨细胞系细胞可恢复且数量增加,且英夫利昔单抗治疗后减少;其次,英夫利昔单抗治疗可缓解早期炎症,但在晚期炎症中允许成熟成骨细胞分化。外周血中成骨细胞系细胞的培养可能是研究脊柱关节炎和其他自身免疫性疾病的一种新方法。