title: Suppression of polyethylene particle-induced osteolysis by exogenous osteoprotegerin.
abstract: Alterations of the key regulators of osteoclastogenesis, receptor activator of NF-kappaB (RANK), RANK ligand (RANKL), and osteoprotegerin (OPG) have been implicated in wear particle-induced osteolysis, the most common cause for implant failure in total joint replacements. This study investigated the effect of exogenous OPG on ultra-high-molecular-weight polyethylene (UHMWPE) particle-induced osteolysis. The murine calvarial osteolysis model was utilized in 28 C57BL/6J mice randomized to four groups. Group I underwent sham surgery only, group II received UHMWPE particles, and group III and IV particles and subcutaneous OPG starting from day 0 (group III) or day 5 (group IV) until sacrifice. After 2 weeks, calvaria were prepared for histology and histomorphometry. Bone resorption was measured within the midline suture using Giemsa staining and osteoclast numbers were determined using TRAP staining. UHMWPE particle implantation resulted in grossly pronounced osteoclastogenesis and bone resorption. Both immediate and delayed treatment with OPG counteracted these particle-induced effects significantly, suppressing osteoclast formation and bone resorption (p < 0.001 and p < 0.001, respectively). In conclusion, exogenous OPG markedly suppressed UHMWPE particle-induced osteolysis in a murine calvarial model. This important finding underscores the crucial significance of the OPG-RANKL-RANK signaling in wear particle-induced osteolysis. Exogenous OPG may prove an effective treatment modality for wear debris-mediated periprosthetic osteolysis after total joint arthroplasty.
authors.affiliation: Department of Orthopaedic Surgery, Kantonsspital Chur, Loestrasse 170, 7000 Chur, Switzerland. fabianvonknoch@yahoo.com
authors.forename: Fabian
authors.initials: F
authors.lastname: von Knoch
authors.forename: Anja
authors.initials: A
authors.lastname: Heckelei
authors.forename: Christian
authors.initials: C
authors.lastname: Wedemeyer
authors.forename: Guido
authors.initials: G
authors.lastname: Saxler
authors.forename: Gero
authors.initials: G
authors.lastname: Hilken
authors.forename: Jochen
authors.initials: J
authors.lastname: Brankamp
authors.forename: Thomas
authors.initials: T
authors.lastname: Sterner
authors.forename: Stefan
authors.initials: S
authors.lastname: Landgraeber
authors.forename: Frank
authors.initials: F
authors.lastname: Henschke
authors.forename: Franz
authors.initials: F
authors.lastname: Löer
authors.forename: Marius
authors.initials: M
authors.lastname: von Knoch
mesh_terms: D000818:Animals; D001672:Biocompatible Materials / Q000378:metabolism; D005260:Female; D006023:Glycoproteins / Q000008:administration & dosage / Q000378:metabolism*; D008297:Male; D008422:Materials Testing; D051379:Mice; D008810:Mice, Inbred C57BL; D008954:Models, Biological; D010010:Osteoclasts / Q000166:cytology / Q000378:metabolism; D010014:Osteolysis; D053244:Osteoprotegerin; D010316:Particle Size; D011095:Polyethylenes / Q000378:metabolism*; D011475:Prosthesis Failure; D011897:Random Allocation; D018160:Receptors, Cytoplasmic and Nuclear / Q000008:administration & dosage / Q000378:metabolism*; D018124:Receptors, Tumor Necrosis Factor / Q000008:administration & dosage / Q000378:metabolism*; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000378:metabolism; D012886:Skull / Q000166:cytology
chemical_list: D001672:Biocompatible Materials; D006023:Glycoproteins; D053244:Osteoprotegerin; D011095:Polyethylenes; D018160:Receptors, Cytoplasmic and Nuclear; D018124:Receptors, Tumor Necrosis Factor; D011994:Recombinant Proteins; C506031:Tnfrsf11b protein, mouse; C111601:ultra-high molecular weight polyethylene