Pro-inflammatory cytokines produced by growth plate chondrocytes may act locally to modulate longitudinal bone growth

Horm Res Paediatr. 2012;77(3):180-7. doi: 10.1159/000337569. Epub 2012 Apr 12.

Abstract

Introduction: Interleukin-1β (IL-1β) and tumour necrosis factor-α (TNF-α), both cytokines upregulated during chronic inflammation, are known to suppress bone growth. So far no role of these cytokines in modulation of normal bone growth has been established.

Methodology: Applying RT-PCR and immunohistochemistry, expression of IL-1β and TNF-α was studied in cultured fetal (E20) rat metatarsal bones. Anakinra (500 μg/ml; IL-1 receptor antagonist) and/or etanercept (500 μg/ml; soluble TNF-α receptor) were used to block cytokine actions.

Results: The local expression of IL-1β and TNF-α was confirmed in the rat metatarsal growth plate. When cultured for 12 days and compared to control, the length of bones exposed to anakinra, etanercept, or anakinra plus etanercept increased by 7.7 ± 2.0 (p < 0.05), 11.7 ± 2.8 (p < 0.01) and 20.3 ± 1.9% (p < 0.001), respectively, while the height of the hypertrophic growth plate zone (collagen X staining) increased by 11.0 ± 6.7, 17.4 ± 7.1 and 43.1 ± 5.0% (p < 0.01), respectively. Moreover, etanercept increased chondrocyte proliferation (BrdU incorporation).

Conclusion: Our findings that IL-1β and TNF-α are produced by growth plate chondrocytes and that their antagonists improve growth of cultured metatarsal bones suggest that these cytokines play a physiological role in the normal regulation of longitudinal bone growth.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bone Development* / drug effects
  • Cell Proliferation / drug effects
  • Chondrocytes / drug effects
  • Chondrocytes / metabolism*
  • Etanercept
  • Growth Plate / metabolism*
  • Immunoglobulin G / pharmacology
  • Interleukin 1 Receptor Antagonist Protein / pharmacology
  • Interleukin-1beta / antagonists & inhibitors
  • Interleukin-1beta / biosynthesis*
  • Metatarsal Bones / drug effects
  • Metatarsal Bones / growth & development
  • Organ Culture Techniques
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Tumor Necrosis Factor
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors
  • Tumor Necrosis Factor-alpha / biosynthesis*

Substances

  • Immunoglobulin G
  • Interleukin 1 Receptor Antagonist Protein
  • Interleukin-1beta
  • Receptors, Tumor Necrosis Factor
  • Tumor Necrosis Factor-alpha
  • Etanercept