Interleukin-17A Inhibition Diminishes Inflammation and New Bone Formation in Experimental Spondyloarthritis

Arthritis Rheumatol. 2019 Apr;71(4):612-625. doi: 10.1002/art.40770. Epub 2019 Feb 18.


Objective: It remains unclear if and how inflammation and new bone formation in spondyloarthritis (SpA) are coupled. We undertook this study to assess the hypothesis that interleukin-17A (IL-17A) is a pivotal driver of both processes.

Methods: The effect of tumor necrosis factor (TNF) and IL-17A on osteogenesis was tested in an osteoblastic differentiation assay using SpA fibroblast-like synoviocytes (FLS) differentiated with dexamethasone, β-glycophosphatase, and ascorbic acid. IL-17A blockade was performed in HLA-B27/human β2 -microglobulin (hβ2 m)-transgenic rats, which served as a model for SpA in both prophylactic and therapeutic settings. Inflammation and new bone formation were evaluated by micro-computed tomography imaging, histologic analysis, and gene expression profiling.

Results: TNF and IL-17A significantly increased in vitro osteoblastic differentiation. In vivo, prophylactic blockade of IL-17A significantly delayed spondylitis and arthritis development and decreased arthritis severity. Anti-IL-17A treatment was also associated with prevention of bone loss and periosteal new bone formation. Therapeutic targeting of IL-17A after the initial inflammatory insult also significantly reduced axial and peripheral joint inflammation. This treatment was again associated with a marked reduction in spinal and peripheral structural damage, including new bone formation. RNA sequencing of target tissue confirmed that IL-17A is a key driver of the molecular signature of disease in this model and that therapeutic anti-IL-17A treatment reversed the inflammatory signature and the selected gene expression related to bone damage.

Conclusion: Both prophylactic and therapeutic inhibition of IL-17A diminished inflammation and new bone formation in HLA-B27/hβ2 m-transgenic rats. Taken together with the ability of IL-17A to promote osteoblastic differentiation of human SpA FLS, these data suggest a direct link between IL-17A-driven inflammation and pathologic new bone formation in SpA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Culture Techniques
  • Cell Differentiation / drug effects*
  • Disease Models, Animal
  • HLA-B27 Antigen / metabolism
  • Humans
  • Inflammation
  • Interleukin-17 / physiology*
  • Osteoblasts / metabolism
  • Osteogenesis / drug effects*
  • Rats
  • Rats, Transgenic
  • Spondylarthritis / drug therapy*
  • Spondylarthritis / physiopathology
  • Synoviocytes / drug effects
  • Tumor Necrosis Factor-alpha / pharmacology*
  • X-Ray Microtomography


  • HLA-B27 Antigen
  • Interleukin-17
  • Tumor Necrosis Factor-alpha