Potential Osteoinductive Effects of Hydroxyapatite Nanoparticles on Mesenchymal Stem Cells by Endothelial Cell Interaction

Nanoscale Research Letters

Haoqi Zhu¹  Ning Gu²  Yu Wang³  Tianlei Han³  Jinxin Tang³  Zhongyi Wang³  Chen Wang³  Yanyang Guo³  Yabing Jin³  Guilan Chen³ 

[1]Department of Physics, City University of Hong Kong, Kowloon, Hong Kong SAR, China

[2]Jiangsu Key Laboratory of Oral Diseases, Department of Laboratory Medicine, Affiliated Hospital of Stomatology, Nanjing Medical University, 210029, Nanjing, China

[3]Jiangsu Key Laboratory of Oral Diseases, Department of Prosthodontics, Affiliated Hospital of Stomatology, Nanjing Medical University, No. 136, Han-zhong Road, 210029, Nanjing, People’s Republic of China

关键词: Hydroxyapatite nanoparticles;    HWJ-MSC;    HUVEC;    HIF-1α;    ERK1/2 pathway;    Two-stage cell-lineage model;   

DOI  :  10.1186/s11671-021-03522-1

来源: Springer

【 摘 要 】

Nano-hydroxyapatite (nano-HA) has attracted substantial attention in the field of regenerative medicine. Endothelial cell (EC)-mesenchymal stem cell (MSC) interactions are necessary for bone reconstruction, but the manner in which nano-HA interacts in this process remains unknown. Herein, we investigated the cytotoxicity and osteoinductive effects of HA nanoparticles (HANPs) on MSCs using an indirect co-culture model mediated by ECs and highlighted the underlying mechanisms. It was found that at a subcytotoxic dose, HANPs increased the viability and expression of osteoblast genes, as well as mineralized nodules and alkaline phosphatase production of MSCs. These phenomena relied on HIF-1α secreted by ECs, which triggered the ERK1/2 signaling cascade. In addition, a two-stage cell-lineage mathematical model was established to quantitatively analyze the impact of HIF-1α on the osteogenic differentiation of MSCs. It demonstrated that HIF-1α exerted a dose-dependent stimulatory effect on the osteogenic differentiation rate of MSCs up to 1500 pg/mL, which was in agreement with the above results. Our data implied that cooperative interactions between HANPs, ECs, and MSCs likely serve to stimulate bone regeneration. Furthermore, the two-stage cell-lineage model is helpful in vitro system for assessing the potential influence of effector molecules in bone tissue engineering.

【 授权许可】

CC BY