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.

Inhibiting wear particles-induced osteolysis with doxycycline

“…So inhibiting osteoclastogenesis and inflammation is an important step in treating wear particles induced by osteolysis. Many efforts have been made to treat or prevent wear particle osteolysis [6,13,[21][22][23][24][25][26] . Until now, only etanercept, a TNFα receptor antagonist and bisphosphonate, has been applied in clinical situations after total joint arthroplasty [26][27][28] .…”

Influence of mouse genetic background on wear particle-induced in vivo inflammatory osteolysis

“…All these were 8-week-old healthy male mice (Shanghai SLAC Laboratory Animal CO. LTD , Shanghai China). Each group was subdivided into a control group receiving a sham operation and a UHMWPE group receiving UHMWPE particles implantation onto calvariae according to previous reported procedures (Table 1) [5,6]. Institutional approval was obtained for all animal procedures.…”

“…Therefore, we hypothesized that different genetic backgrounds in mice could influence in vivo reaction to UH-MWPE wear particles, which might give some clues to patients differences in response to joint replacement. We used a previously reported model for in vivo mouse calvarial wear particle-induced osteolysis to study the influence of genetic backgrounds on wear particle-induced osteolysis [5,6].…”

Inhibitory effect of (-)-epigallocatechin gallate on titanium particle-induced TNF-α release andin vivoosteolysis

“…Erythromycin, a 14-membered lactone ring macrolide antibiotic, also dramatically reduces UHMWPE particle-induced tissue inflammation in vivo and inhibits osteoclast formation and function in vitro (Ren et al, 2006). Exogenouslyadministered osteoprotegerin (OPG), a decoy receptor of RANKL, can prevent and treat polyethylene particle-induced osteolysis in a murine calvarial model (von Knoch et al, 2005b). Recent reports demonstrate that VIVD (a peptide inhibitor of a nuclear factor of activated T cells) and AM630 (a cannabinoid receptor-selective antagonist) suppress Ti particle-induced inflammatory cytokines and osteoclast formation in vitro (Liu et al, 2009).…”