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Autophagy mediated CoCrMo particle-induced peri-implant osteolysis by promoting osteoblast apoptosis.

Wang Z, Liu N, Liu K, Zhou G, Gan J, Wang Z, Shi T, He W, Wang L, Guo T, Bao N, Wang R, Huang Z, Chen J, Dong L, Zhao J, Zhang J - Autophagy (2015)

Bottom Line: Both autophagy inhibitor 3-MA (3-methyladenine) and siRNA of Atg5 could dramatically reduce CoPs-induced apoptosis in osteoblasts.Further, inhibition of autophagy with 3-MA ameliorated the severity of osteolysis in PIO animal models.Moreover, 3-MA also prevented osteoblast apoptosis in an antiautophagic way when tested in PIO model.

View Article: PubMed Central - PubMed

Affiliation: a Jinling Hospital; Department of Orthopaedics; State Key Laboratory of Pharmaceutical Biotechnology; Nanjing University ; Nanjing , China.

ABSTRACT
Wear particle-induced osteolysis is the leading cause of aseptic loosening, which is the most common reason for THA (total hip arthroplasty) failure and revision surgery. Although existing studies suggest that osteoblast apoptosis induced by wear debris is involved in aseptic loosening, the underlying mechanism linking wear particles to osteoblast apoptosis remains almost totally unknown. In the present study, we investigated the effect of autophagy on osteoblast apoptosis induced by CoCrMo metal particles (CoPs) in vitro and in a calvarial resorption animal model. Our study demonstrated that CoPs stimulated autophagy in osteoblasts and PIO (particle-induced osteolysis) animal models. Both autophagy inhibitor 3-MA (3-methyladenine) and siRNA of Atg5 could dramatically reduce CoPs-induced apoptosis in osteoblasts. Further, inhibition of autophagy with 3-MA ameliorated the severity of osteolysis in PIO animal models. Moreover, 3-MA also prevented osteoblast apoptosis in an antiautophagic way when tested in PIO model. Collectively, these results suggest that autophagy plays a key role in CoPs-induced osteolysis and that targeting autophagy-related pathways may represent a potential therapeutic approach for treating particle-induced peri-implant osteolysis.

No MeSH data available.


Related in: MedlinePlus

The autophagy inhibitor 3-MA ameliorates CoPs-induced mouse calvarial osteolysis assessed by micro-CT. (A) Representative images of micro-CT with 3-dimensional reconstructed images from each group (left). Cross-sectional views of the reconstructed images were indicated by the white horizontal line in the left panel, and the bone osteolysis sites are indicated by white arrows (right). (B) BV/TV and percentage of total porosity of each sample were measured. Values are expressed as means ± S.E.M. n = 7 mice per group. *, P < 0.05, vs. sham; #, P < 0.05 vs. CoPs group.
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f0006: The autophagy inhibitor 3-MA ameliorates CoPs-induced mouse calvarial osteolysis assessed by micro-CT. (A) Representative images of micro-CT with 3-dimensional reconstructed images from each group (left). Cross-sectional views of the reconstructed images were indicated by the white horizontal line in the left panel, and the bone osteolysis sites are indicated by white arrows (right). (B) BV/TV and percentage of total porosity of each sample were measured. Values are expressed as means ± S.E.M. n = 7 mice per group. *, P < 0.05, vs. sham; #, P < 0.05 vs. CoPs group.

Mentions: The osteolysis induced by CoPs implantation was examined by micro-CT (micro-CT) with 3-dimensional reconstruction. Figure 6A demonstrated that CoPs-induced osteolysis was suppressed by cotreatment with 3-MA. Quantitative analysis of bone parameters further confirmed that 3-MA markedly ameliorated the BV/TV (bone volume/total volume) and decreased the percentage of total porosity that induced by CoPs (Fig. 6B and C).Figure 6.


Autophagy mediated CoCrMo particle-induced peri-implant osteolysis by promoting osteoblast apoptosis.

Wang Z, Liu N, Liu K, Zhou G, Gan J, Wang Z, Shi T, He W, Wang L, Guo T, Bao N, Wang R, Huang Z, Chen J, Dong L, Zhao J, Zhang J - Autophagy (2015)

The autophagy inhibitor 3-MA ameliorates CoPs-induced mouse calvarial osteolysis assessed by micro-CT. (A) Representative images of micro-CT with 3-dimensional reconstructed images from each group (left). Cross-sectional views of the reconstructed images were indicated by the white horizontal line in the left panel, and the bone osteolysis sites are indicated by white arrows (right). (B) BV/TV and percentage of total porosity of each sample were measured. Values are expressed as means ± S.E.M. n = 7 mice per group. *, P < 0.05, vs. sham; #, P < 0.05 vs. CoPs group.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4835204&req=5

f0006: The autophagy inhibitor 3-MA ameliorates CoPs-induced mouse calvarial osteolysis assessed by micro-CT. (A) Representative images of micro-CT with 3-dimensional reconstructed images from each group (left). Cross-sectional views of the reconstructed images were indicated by the white horizontal line in the left panel, and the bone osteolysis sites are indicated by white arrows (right). (B) BV/TV and percentage of total porosity of each sample were measured. Values are expressed as means ± S.E.M. n = 7 mice per group. *, P < 0.05, vs. sham; #, P < 0.05 vs. CoPs group.
Mentions: The osteolysis induced by CoPs implantation was examined by micro-CT (micro-CT) with 3-dimensional reconstruction. Figure 6A demonstrated that CoPs-induced osteolysis was suppressed by cotreatment with 3-MA. Quantitative analysis of bone parameters further confirmed that 3-MA markedly ameliorated the BV/TV (bone volume/total volume) and decreased the percentage of total porosity that induced by CoPs (Fig. 6B and C).Figure 6.

Bottom Line: Both autophagy inhibitor 3-MA (3-methyladenine) and siRNA of Atg5 could dramatically reduce CoPs-induced apoptosis in osteoblasts.Further, inhibition of autophagy with 3-MA ameliorated the severity of osteolysis in PIO animal models.Moreover, 3-MA also prevented osteoblast apoptosis in an antiautophagic way when tested in PIO model.

View Article: PubMed Central - PubMed

Affiliation: a Jinling Hospital; Department of Orthopaedics; State Key Laboratory of Pharmaceutical Biotechnology; Nanjing University ; Nanjing , China.

ABSTRACT
Wear particle-induced osteolysis is the leading cause of aseptic loosening, which is the most common reason for THA (total hip arthroplasty) failure and revision surgery. Although existing studies suggest that osteoblast apoptosis induced by wear debris is involved in aseptic loosening, the underlying mechanism linking wear particles to osteoblast apoptosis remains almost totally unknown. In the present study, we investigated the effect of autophagy on osteoblast apoptosis induced by CoCrMo metal particles (CoPs) in vitro and in a calvarial resorption animal model. Our study demonstrated that CoPs stimulated autophagy in osteoblasts and PIO (particle-induced osteolysis) animal models. Both autophagy inhibitor 3-MA (3-methyladenine) and siRNA of Atg5 could dramatically reduce CoPs-induced apoptosis in osteoblasts. Further, inhibition of autophagy with 3-MA ameliorated the severity of osteolysis in PIO animal models. Moreover, 3-MA also prevented osteoblast apoptosis in an antiautophagic way when tested in PIO model. Collectively, these results suggest that autophagy plays a key role in CoPs-induced osteolysis and that targeting autophagy-related pathways may represent a potential therapeutic approach for treating particle-induced peri-implant osteolysis.

No MeSH data available.


Related in: MedlinePlus