Genes differentially expressed in titanium implant healing.

Bone generation occurs around titanium implants; however, its underlying mechanisms are unknown. We hypothesized that molecular determinants distinct from those undertaking normal bone healing regulate osseointegration. Using differential display-polymerase chain-reaction in the male rat model, we isolated 3 genes that are differentially expressed in bone healing with implants, but not in osteotomy healing. A homology search indicated that these 3 genes are apolipoprotein E, prolyl 4-hydroxylase alpha-subunit, and an unknown transcript. Differential expression of these genes was remarkable during early healing stages up to week 2, and accelerated with rough acid-etched surfaces compared with machined surfaces. The differential expression was confirmed in the female rats, with enhanced expression for the acid-etched surfaces. The osseointegration-unfavorable condition created by gonadal estrogen deficiency reduced the level of differential expression. This study provides evidence that selected gene transcripts are induced by titanium implants under regulatory control strongly associated with the nature of osseointegration.