Alpha-calcitonin gene-related peptide can reverse the catabolic influence of UHMWPE particles on RANKL expression in primary human osteoblasts

Int J Biol Sci. 2010 Sep 15;6(6):525-36. doi: 10.7150/ijbs.6.525.


Background and purpose: A linkage between the neurotransmitter alpha-calcitonin gene-related peptide (alpha-CGRP) and particle-induced osteolysis has been shown previously. The suggested osteoprotective influence of alpha-CGRP on the catabolic effects of ultra-high molecular weight polyethylene (UHMWPE) particles is analyzed in this study in primary human osteoblasts.

Methods: Primary human osteoblasts were stimulated by UHMWPE particles (cell/particle ratios 1:100 and 1:500) and different doses of alpha-CGRP (10(-7 )M, 10(-9 )M, 10(-11 )M). Receptor activator of nuclear factor-κB ligand (RANKL) and osteoprotegerin (OPG) mRNA expression and protein levels were measured by RT-PCR and Western blot.

Results: Particle stimulation leads to a significant dose-dependent increase of RANKL mRNA in both cell-particle ratios and a significant down-regulation of OPG mRNA in cell-particle concentrations of 1:500. A significant depression of alkaline phosphatase was found due to particle stimulation. Alpha-CGRP in all tested concentrations showed a significant depressive effect on the expression of RANKL mRNA in primary human osteoblasts under particle stimulation. Comparable reactions of RANKL protein levels due to particles and alpha-CGRP were found by Western blot analysis. In cell-particle ratios of 1:100 after 24 hours the osteoprotective influence of alpha-CGRP reversed the catabolic effects of particles on the RANKL expression.

Interpretation: The in-vivo use of alpha-CGRP, which leads to down-regulated RANKL in-vitro, might inhibit the catabolic effect of particles in conditions of particle induced osteolysis.

Keywords: Aseptic loosening; RANKL.; alpha-CGRP; hOB; polyethylene.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blotting, Western
  • Calcitonin Gene-Related Peptide / pharmacology*
  • Cells, Cultured
  • Gene Expression Regulation / drug effects*
  • Humans
  • Middle Aged
  • Osteoblasts / drug effects*
  • Osteoblasts / metabolism*
  • Polyethylenes / pharmacology*
  • RANK Ligand / genetics
  • RANK Ligand / metabolism*
  • Reverse Transcriptase Polymerase Chain Reaction


  • Polyethylenes
  • RANK Ligand
  • TNFSF11 protein, human
  • ultra-high molecular weight polyethylene
  • Calcitonin Gene-Related Peptide