Upregulation of BMP-2 expression in peripheral blood mononuclear cells by proinflammatory cytokines and radiographic progression in ankylosing spondylitis

Mod Rheumatol. 2015;25(6):913-8. doi: 10.3109/14397595.2015.1029221. Epub 2015 Apr 30.

Abstract

Objectives: To investigate the effect of inflammation on expressions of bone morphogenetic proteins (BMPs) in peripheral blood mononuclear cells (PBMCs) and its association with individual radiographic changes in patients with ankylosing spondylitis (AS).

Methods: The changes in BMP-2, -4, and -7 gene expressions in PBMCs were measured after stimulation by tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β). The correlation of increase in gene expression with clinical and radiographic findings in patients with AS were analyzed.

Results: Both TNF-α and IL-1β could enhance BMP-2 expression in PBMCs from AS patients. Increases in BMP-2, -4, and -7 expressions in PBMCs positively correlated with total modified Stoke Ankylosing Spondylitis Spinal Score (all p < 0.05). Moreover, increases in BMP-2, -4, and -7 gene expressions after TNF-α and IL-1β stimulation were greater among AS patients with versus without severe sacroiliitis (all p < 0.05). Increases in BMP-2 and -7 expressions were greater in PBMCs from 4 patients with total (cervical, thoracic, and lumbar) spinal ankylosis than in the 8 patients who did not have total spinal ankylosis (all p < 0.05).

Conclusions: In AS, inflammation upregulates the expression of BMPs in PBMCs which may lead to the radiographic progression with new bone formation.

Keywords: Ankylosing spondylitis; Bone morphogenetic protein; Inflammation; Interleukin-1β; Tumor necrosis factor-α.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Bone Morphogenetic Protein 2 / genetics
  • Bone Morphogenetic Protein 2 / metabolism*
  • Bone Morphogenetic Protein 4 / genetics
  • Bone Morphogenetic Protein 4 / metabolism
  • Bone Morphogenetic Protein 7 / genetics
  • Bone Morphogenetic Protein 7 / metabolism
  • Disease Progression
  • Female
  • Gene Expression / drug effects
  • Humans
  • Interleukin-1beta / pharmacology
  • Leukocytes, Mononuclear / drug effects
  • Leukocytes, Mononuclear / metabolism*
  • Male
  • Middle Aged
  • Radiography
  • Spondylitis, Ankylosing / diagnostic imaging
  • Spondylitis, Ankylosing / genetics
  • Spondylitis, Ankylosing / metabolism*
  • Tumor Necrosis Factor-alpha / pharmacology
  • Up-Regulation*
  • Young Adult

Substances

  • BMP2 protein, human
  • BMP4 protein, human
  • BMP7 protein, human
  • Bone Morphogenetic Protein 2
  • Bone Morphogenetic Protein 4
  • Bone Morphogenetic Protein 7
  • Interleukin-1beta
  • Tumor Necrosis Factor-alpha