Histological Evidence of Increased Osteoclast Cell Number and Asymmetric Bone Resorption Activity in the Tibiae of Interleukin-6-Deficient Mice

J Histochem Cytochem. 2014 Aug;62(8):556-64. doi: 10.1369/0022155414537830. Epub 2014 May 14.

Abstract

Interleukin-6 (IL-6) is a multifunctional cytokine considered to modulate bone homeostasis. Based on previous contradictory studies, we aimed to verify the influence of IL-6 deficiency on bone remodeling using an IL-6 knockout (IL-6-/-) murine model. Eight-month-old male mice, homozygous for the disrupted IL-6 gene, and their wild type (WT) littermates (control), were used. After transcardiac perfusion, tibiae were removed for histochemical analysis. Compared with the control group, IL-6 deficiency increased tartrate resistant acid phosphatase (TRAP)-positive osteoclast numbers and up-regulated the alkaline phosphatase (ALP) activity of osteoblasts in the metaphysis of the tibia. However, further analysis of serial histological sections from IL-6-/- mice found a significant discrepancy in osteoclast number, with the higher number of TRAP-positive osteoclasts conflicting with the lower number of cathepsin K-positive osteoclasts. Moreover, TUNEL staining identified a significantly higher rate of osteoclast apoptosis in IL-6-/- mice as compared with their WT controls. IL-6 deficiency induced abundant TRAP-positive osteoclasts but delayed bone remodeling by significantly inhibiting the bone resorption activity of osteoclasts and promoting osteoclast apoptosis.

Keywords: IL-6; apoptosis; bone resorption; osteoblast; osteoclast.

MeSH terms

  • Alkaline Phosphatase / metabolism
  • Animals
  • Apoptosis
  • Bone Remodeling
  • Bone Resorption / pathology*
  • Bone Resorption / physiopathology
  • Cell Count
  • Interleukin-6 / genetics*
  • Male
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Osteoblasts / pathology
  • Osteoclasts / pathology*
  • Tartrate-Resistant Acid Phosphatase / metabolism
  • Tibia / pathology*

Substances

  • Interleukin-6
  • Alkaline Phosphatase
  • Tartrate-Resistant Acid Phosphatase