Defect-related luminescent bur-like hydroxyapatite microspheres induced apoptosis of MC3T3-E1 cells by lysosomal and mitochondrial pathways
- 101 Downloads
When orthopedic joints coated by hydroxyapatite (HA) were implanted in the human body, they release wear debris into the surrounding tissues. The generation and accumulation of wear particles will induce aseptic loosening. However, the potential bioeffect and mechanism of HA-coated orthopedic implants on bone cells are poorly understood. In this study, defect-related luminescent bur-like hydroxyapatite (BHA) microspheres with the average diameter of 7–9 μm which are comparable to that of the wear-debris particles from aseptically loosened HA implants or HA debris have been synthesized by hydrothermal synthesis and the MC3T3-E1 cells were set as a cells model to study the potential bioeffect and mechanism of BHA microspheres. The studies demonstrated that BHA microspheres could be taken into MC3T3-E1 cells via endocytosis involved in micropinocytosis- and clathrin-mediated endocytosis process, and exert cytotoxicity effect. BHA microspheres could induce the cell apoptosis by intracellular production of reactive oxygen species (ROS), which led to not only an increase in the permeability of lysosome and release of cathepsins B, but also mitochondrial dysfunction and DNA damage. Our results provide novel evidence to elucidate their toxicity mechanisms and might be helpful for more reasonable applications of HA-based orthopaedic implants in the future.
Keywordsdefect-related luminescence hydroxyapatite microspheres osteoblasts apoptosis
Unable to display preview. Download preview PDF.
This work was supported by the National Natural Science Foundation of China (21301046, 51302062), the Natural Science Foundation of Hebei Province (B2017201125, B2017201100), the Second Batch of Top Youth Talent Support Program of Hebei Province and Distinguished Young Scholars Fund of Hebei University (2015JQ04).
- Doostmohammadi, A., Monshi, A., Salehi, R., Hossein Fathi, M., Seyedjafari, E., Shafiee, A., and Soleimani, M. (2011). Cytotoxicity evaluation of 63s bioactive glass and bone-derived hydroxyapatite particles using human bone-marrow stem cells. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub 155, 323–326.CrossRefPubMedGoogle Scholar
- Fang, L., Neutzner, A., Turtschi, S., Flammer, J., and Mozaffarieh, M. (2015). Comet assay as an indirect measure of systemic oxidative stress. J Vis Exp 22, e52763.Google Scholar
- Guicciardi, M.E., Deussing, J., Miyoshi, H., Bronk, S.F., Svingen, P.A., Peters, C., Kaufmann, S.H., and Gores, G.J. (2000). Cathepsin B contributes to TNF-a-mediated hepatocyte apoptosis by promoting mitochondrial release of cytochrome c. J Clin Invest 106, 1127–1137.CrossRefPubMedPubMedCentralGoogle Scholar
- Huerta-García, E., Pérez-Arizti, J.A., Márquez-Ramírez, S.G., Delgado-Buenrostro, N.L., Chirino, Y.I., Iglesias, G.G., and López-Marure, R. (2014). Titanium dioxide nanoparticles induce strong oxidative stress and mitochondrial damage in glial cells. Free Radic Biol Med 73, 84–94.CrossRefPubMedGoogle Scholar
- Kido, H.W., Ribeiro, D.A., de Oliveira, P., Parizotto, N.A., Camilo, C.C., Fortulan, C.A., Marcantonio Jr., E., da Silva, V.H.P., and Muniz Renno, A.C. (2014). Biocompatibility of a porous alumina ceramic scaffold coated with hydroxyapatite and bioglass. J Biomed Mater Res 102, 2072–2078.CrossRefGoogle Scholar
- Oberle, C., Huai, J., Reinheckel, T., Tacke, M., Rassner, M., Ekert, P.G., Buellesbach, J., and Borner, C. (2010). Lysosomal membrane permeabilization and cathepsin release is a Bax/Bak-dependent, amplifying event of apoptosis in fibroblasts and monocytes. Cell Death Differ 17, 1167–1178.CrossRefPubMedGoogle Scholar
- Roussi, S., Gossé, F., Aoudé-Werner, D., Zhang, X., Marchioni, E., Geoffroy, P., Miesch, M., and Raul, F. (2007). Mitochondrial perturbation, oxidative stress and lysosomal destabilization are involved in 7β-hydroxysitosterol and 7β-hydroxycholesterol triggered apoptosis in human colon cancer cells. Apoptosis 12, 87–96.CrossRefPubMedGoogle Scholar
- Yadavilli, S., Martinez-Ceballos, E., Snowden-Aikens, J., Hurst, A., Joseph, T., Albrecht, T., and Muganda, P.M. (2007). Diepoxybutane activates the mitochondrial apoptotic pathway and mediates apoptosis in human lymphoblasts through oxidative stress. Toxicol In Vitro 21, 1429–1441.CrossRefPubMedPubMedCentralGoogle Scholar
- Zhang, S., Chen, S., Gao, C., Jin, Y., Jia, G., J., Li, Z., Liu, D. Liang, X., Yang, X., and Zhang, J. (2017). Apoptosis induced by NaYF4:Eu3+ nanoparticles in liver cells via mitochondria damage dependent pathway. Sci China Chem 60, 1–8.Google Scholar