Size-Dependent Cytotoxicity of Hydroxyapatite Crystals on Renal Epithelial Cells

• Published in: International journal of nanomedicine Vol. 15; pp. 5043 - 5060
• Main Authors: Sun, Xin-Yuan, Chen, Jia-Yun, Rao, Chen-Ying, Ouyang, Jian-Ming
• Format: Journal Article
• Language: English
• Published: New Zealand Dove Medical Press Limited 01-01-2020; Dove; Dove Medical Press
• Subjects: Calcium Oxalate - chemistry; Cell Cycle - drug effects; cell injury; Cell Line; crystal size; cytotoxicity; Cytotoxins - chemistry; Cytotoxins - toxicity; Durapatite - chemistry; Durapatite - toxicity; Epithelial Cells - cytology; Epithelial Cells - drug effects; Epithelial Cells - metabolism; Humans; hydroxyapatite; Hydroxyapatites; Kidney - cytology; Kidney stones; Membrane Potential, Mitochondrial - drug effects; nanocrystal; Original Research; Oxalates; Oxalic acid; Reactive Oxygen Species - metabolism; China; hydroxyapatite; nanocrystal; cell injury; crystal size; cytotoxicity
• ISSN: 1178-2013; 1176-9114; 1178-2013
• DOI: 10.2147/IJN.S232926

Hydroxyapatite (HAP) is a common component of most idiopathic calcium oxalate (CaOx) stones and is often used as a nidus to induce the formation of CaOx kidney stones.
This work comparatively studies the cytotoxicity of four kinds of HAP crystals with different sizes (40 nm to 2 μm), namely, HAP-40 nm, HAP-70 nm, HAP-1 μm, and HAP-2 μm, on human renal proximal tubular epithelial cells (HK-2).
HAP crystals reduce the viability and membrane integrity of HK-2 cells in a concentration-dependent manner and consequently cause cytoskeleton damage, cell swelling, increased intracellular reactive oxygen species level, decreased mitochondrial membrane potential, increased intracellular calcium concentration, blocked cell cycle and stagnation in G0/G1 phase, and increased cell necrosis rate. HAP toxicity to HK-2 cells increases with a decrease in crystal size.
Cell damage caused by HAP crystals increases the risk of kidney stone formation.