Size-Dependent Cytotoxicity of Hydroxyapatite Crystals on Renal Epithelial Cells

Abstract

Xin-Yuan Sun, Jia-Yun Chen, Chen-Ying Rao, Jian-Ming Ouyang Department of Chemistry, Institute of Biomineralization and Lithiasis Research, Jinan University, Guangzhou 510632, People’s Republic of ChinaCorrespondence: Jian-Ming OuyangDepartment of Chemistry Institute of Biomineralization and Lithiasis Research,Jinan University, Guangzhou 510632, People’s Republic of ChinaTel [phone]Email [email protected]: 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.Methods: 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).Results: 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.Conclusion: Cell damage caused by HAP crystals increases the risk of kidney stone formation.Keywords: cytotoxicity, nanocrystal, hydroxyapatite, crystal size, cell injury

Keywords

• cytotoxicity
• nanocrystal
• hydroxyapatite
• crystal size
• cell injury