title: The potential role of fibroblasts in periprosthetic osteolysis: fibroblast response to titanium particles.
abstract: Periprosthetic osteolysis with or without aseptic loosening is a major clinical problem in total hip arthroplasty. While the macrophage response to prosthetic wear debris and its role in periprosthetic osteolysis has been extensively studied, information regarding other cell types (fibroblasts, osteoblasts) is limited. This study explored the response of fibroblasts to particulate wear debris. Fibroblasts isolated from interfacial membranes of patients with failed total hip replacements and normal synovial tissue, when challenged with small-sized ( < 3 microns) titanium (Ti) particles, responded with significantly enhanced expressions of collagenase, stromelysin and, to a much lesser extent, their tissue inhibitor of metalloproteinases (TIMP). These "regulated" expressions at both mRNA and protein levels were correlated with the size and composition of particles. De novo protein synthesis was required for the regulation of these mRNAs. A similar effect could be induced by the treatment of the cells with particle-free conditioned medium from 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-resorbing metalloproteinases and mediator(s) which resulted in suppressed collagen synthesis in osteoblasts.
authors.affiliation: Department of Biochemistry, Rush Medical College, Rush-Presbyterian-St. Luke's Medical Center, Chicago, Illinois, USA.
authors.forename: J
authors.initials: J
authors.lastname: Yao
authors.forename: T T
authors.initials: TT
authors.lastname: Glant
authors.forename: M W
authors.initials: MW
authors.lastname: Lark
authors.forename: K
authors.initials: K
authors.lastname: Mikecz
authors.forename: J J
authors.initials: JJ
authors.lastname: Jacobs
authors.forename: N I
authors.initials: NI
authors.lastname: Hutchinson
authors.forename: L A
authors.initials: LA
authors.lastname: Hoerrner
authors.forename: K E
authors.initials: KE
authors.lastname: Kuettner
authors.forename: J O
authors.initials: JO
authors.lastname: Galante
mesh_terms: D001483:Base Sequence; D001862:Bone Resorption / Q000201:enzymology; D005347:Fibroblasts / Q000187:drug effects / Q000502:physiology; D006622:Hip Prosthesis / Q000009:adverse effects*; D006801:Humans; D008666:Metalloendopeptidases / Q000378:metabolism; D008969:Molecular Sequence Data; D010014:Osteolysis / Q000473:pathology*; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000378:metabolism; D012016:Reference Values; D013268:Stimulation, Chemical; D013583:Synovial Membrane / Q000473:pathology*; D014025:Titanium / Q000009:adverse effects*
chemical_list: D012333:RNA, Messenger; D014025:Titanium; D008666:Metalloendopeptidases