title: Murine model of prosthesis failure for the long-term study of aseptic loosening.
abstract: We examined a novel mouse model of wear debris-induced prosthesis instability and osteolysis, and its application for the evaluation of therapy. A stainless steel or titanium-alloy pin was implanted into the proximal tibia to form a contiguous surface with the articular cartilage. In some mice, titanium particles were injected into the tibial canal during the surgery, followed by monthly intraarticular injection. MicroCT scans revealed that the implants without particle challenge were stable without bone mineral density changes for 6 months. Histological analysis showed new bone formation around the implant at 6 weeks postsurgery. Periprosthetic soft tissue with inflammatory cells was a ubiquitous finding at the interface between the implant and surrounding bone in samples exposed to titanium particles, and expression of IL-1beta, TNFalpha, and CD68 was common in these joints. Pullout tests indicated that an average 5N load was required to pull out stable implants from surrounding bone. However, particle stimulation dramatically reduced the pullout force to less than 0.4 N. The feasibility of in vivo gene transfer on this model was confirmed by X-gal staining of synovial membrane and periprosthetic tissue after injection of AAV-LacZ in the prosthetic joint. This murine model of weight-bearing knee prosthesis provides an economical, reproducible, and easily obtained means to study joint arthroplasty failure. The ability to evaluate the biomechanical properties of the prosthetic joint, in addition to histological and biochemical examination, results in a useful model to investigate many of the properties of prosthetic joint components during the response to debris-associated osteolysis.
authors.affiliation: Department of Orthopaedic Surgery, Wayne State University, and the John D. Dingell VA Medical Center, UHC-7C, 4201 St. Antoine Boulevard, Detroit, Michigan 48201, USA. syang@wayne.edu
authors.forename: Shang-You
authors.initials: SY
authors.lastname: Yang
authors.forename: Haiying
authors.initials: H
authors.lastname: Yu
authors.forename: Weiming
authors.initials: W
authors.lastname: Gong
authors.forename: Bin
authors.initials: B
authors.lastname: Wu
authors.forename: Lois
authors.initials: L
authors.lastname: Mayton
authors.forename: Richard
authors.initials: R
authors.lastname: Costello
authors.forename: Paul H
authors.initials: PH
authors.lastname: Wooley
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D001858:Bone Nails; D001862:Bone Resorption / Q000000981:diagnostic imaging / Q000209:etiology* / Q000628:therapy; D004195:Disease Models, Animal; D015316:Genetic Therapy / Q000379:methods; D053583:Interleukin-1beta / Q000378:metabolism; D007720:Knee Prosthesis; D007763:Lac Operon; D051379:Mice; D008807:Mice, Inbred BALB C; D011475:Prosthesis Failure; D013193:Stainless Steel; D014025:Titanium; D014057:Tomography, X-Ray Computed; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D000097382:CD68 Molecule
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D053583:Interleukin-1beta; D013193:Stainless Steel; D014025:Titanium; D014409:Tumor Necrosis Factor-alpha; C081026:CD68 protein, mouse; D000097382:CD68 Molecule