title: Titanium implants induce expression of matrix metalloproteinases in bone during osseointegration.
abstract: Implanted pure titanium fixtures are able to completely integrate with bone, in part because of the formation of a strong extracellular matrix (ECM) bond at the titanium-bone interface. In this study, we used a rodent femur model of intramedullary osseointegration to analyze the changes in immunoreactivity of ECM-controlling matrix metalloproteinases (MMPs), tissue inhibitor of metalloproteinase-3 (TIMP-3), and tumor necrosis factor alpha (TNF-alpha) during osseointegration. We observed dramatic increases in MMP-2, MMP-9, MMP-7, TIMP-3, and TNF-alpha in osteocytes, osteoclasts, haversian canals, and the interface matrix in bone ipsilateral to the titanium implant. An increase in TIMP-3, MMP-9, and MMP-7 in hypertrophied chondrocytes and the vascular component of the epiphysial growth plate was also observed in experimental bone. These findings were not seen in contralateral or sham-operated bone, where the titanium fixtures were threaded into the femur and immediately removed. Our data link titanium-induced bone remodeling to changes in expression and distribution of MMPs.
authors.affiliation: San Diego Department of Veterans Affairs Healthcare System, San Diego, CA, USA. vshubayev@ucsd.edu
authors.forename: Veronica I
authors.initials: VI
authors.lastname: Shubayev
authors.forename: Rickard
authors.initials: R
authors.lastname: Brånemark
authors.forename: Joanne
authors.initials: J
authors.lastname: Steinauer
authors.forename: Robert R
authors.initials: RR
authors.lastname: Myers
mesh_terms: D000818:Animals; D008297:Male; D020782:Matrix Metalloproteinases / Q000096:biosynthesis*; D016348:Osseointegration; D019736:Prostheses and Implants; D051381:Rats; D017207:Rats, Sprague-Dawley; D014025:Titanium / Q000494:pharmacology*
chemical_list: D014025:Titanium; D020782:Matrix Metalloproteinases