The effect of shock wave therapy on gene expression in human osteoblasts isolated from hypertrophic fracture non-unions

Abstract

Shockwavetherapyhasbeenincreasinglyevalu- atedasanon-invasivealternativeforthetreatmentofdelayed fracture healing and non-unions. Although several clinical studies showed a beneficial effect especially for the hyper- trophictypeofnon-union,littleisknownaboutthebiological mechanismofitsosteogeniceffect.Toidentifythemolecular background for the positive effect of shock waves on heal- ing of fracture non-unions, we have analyzed the changes of the global gene expression in human osteoblasts after exposure to shock waves of different energy flux densities. Human osteoblasts were isolated from five patients at non- unionsites,treatedwith500impulsesofenergyfluxdensities of 0.06 and 0.5mJ/mm 2 , and cultured for 96 h. Affymetrix HG-U133A microarrays were used for the analysis of the shock wave-regulated mRNA-transcripts. Differential gene expression was verified by reverse transcriptase polymerase chain reactions. We identified 47 transcripts that showed dif- ferential expression after 0.06mJ/mm 2 and 45 transcripts after 0.5mJ/mm 2 energy treatment. Most intriguing was the up-regulation of neprilysin, calmegin, osteoglycin, asporin, and interleukin-13 receptor-α2. Eighteen identified genes were previously described to fulfill an important function in bone growth and metabolism. Our study provides the