THE POTENTIAL ROLE OF FIBROBLASTS IN PERIPROSTHETIC OSTEOLYSIS - FIBROBLAST RESPONSE TO TITANIUM PARTICLES

Periprosthetic osteolysis with or without aseptic loosening is a major clinical problem in total hip arthroplasty, While the macrophage resp onse to prosthetic wear debris and its role in periprosthetic osteolys is has been extensively studied, information regarding other cell type s (fibroblasts, osteoblasts) is limited, This study explored the respo nse of fibroblasts to particulate wear debris, Fibroblasts isolated fr om interfacial membranes of patients with failed total hip replacement s and normal synovial tissue, when challenged with small-sized (<3 mu m) titanium (Ti) particles, responded with significantly enhanced expr essions of collagenase, stromelysin and, to a much lesser extent, thei r tissue inhibitor of metalloproteinases (TIMP), These ''regulated'' e xpressions at both mRNA and protein levels were correlated with the si ze and composition of particles, De novo protein synthesis was require d for the regulation of these mKNAs, A similar effect could be induced by the treatment of the cells with particle-free conditioned medium f rom Ti particle-stimulated fibroblasts. Furthermore, this conditioned medium significantly suppressed the mRNA levels of procollagen alpha(1 )(I) and alpha(1)(III) in osteoblast-like MG-63 cells, It is concluded that fibroblasts stimulated with certain particle debris may play an important role in periprosthetic osteolysis by releasing bone-resorbin g metalloproteinases and mediator(s) which resulted in suppressed coll agen synthesis in osteoblasts.