Suppression of polyethylene particle-induced osteolysis by exogenous osteoprotegerin.
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.
von Knoch
Fabian
F
Department of Orthopaedic Surgery, Kantonsspital Chur, Loestrasse 170, 7000 Chur, Switzerland. fabianvonknoch@yahoo.com
Heckelei
Anja
A
Wedemeyer
Christian
C
Saxler
Guido
G
Hilken
Gero
G
Brankamp
Jochen
J
Sterner
Thomas
T
Landgraeber
Stefan
S
Henschke
Frank
F
Löer
Franz
F
von Knoch
Marius
M
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
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