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Logo for the Journal of Rehab R and D
Volume 41 Number 6A, November/December 2004
Pages 757 — 766


Titanium implants induce expression of matrix metalloproteinases in bone during osseointegration

Veronica I. Shubayev, MD; Rickard Brånemark, MD, PhD; Joanne Steinauer, BS; Robert R. Myers, PhD

San Diego Department of Veterans Affairs Healthcare System, San Diego, CA; University of California, San Diego, School of Medicine, Department of Anesthesiology, San Diego, CA; The Institute for Applied Biotechnology,
Gothenburg, Sweden
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.

Key words: bone, endosteal, histopathology, intramedullary, matrix, MMP, osseointegration, TIMP, titanium, TNF.

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