Effect of hydroxyapatite nanoparticles and wedelolactone on osteoblastogenesis from bone marrow mesenchymal stem cells

Abstract

Regenerative medicine has a high demand for the development of scaffold materials combined with other osteogenic inducers to generate bioactive composite materials for bone replacement therapies. Previously, we reported that wedelolactone promoted osteoblastogenesis of bone marrow mesenchymal stem cells (BMSCs). In this study, the effect of hydroxyapatites (HAps), bone composite materials we prepared, and the combined effect of wedelolactone and HAps on osteoblastogenesis differentiation was first evaluated. Three kinds of HAps constructed by a rod-like shape with particle size of 25 nm (HAp-1), 37 nm (HAp-2), and 33 nm (HAp-3) did not affect BMSC survival, but induced activity of alkaline phosphatase(ALP), a marker enzyme for osteoblastogenesis. HAp-1 treatment resulted in a more significant increase in the number of ALP staining-positive BMSC, and maintained an extended time for the increased number of ALP staining-positive BMSC. Moreover, HAp-1 combined with wedelolactone induced a higher ALP activity for a longer time than HAp-2 and HAp-3, and also increased the bone mineralization level. Osteoblastogenesis-related marker genes expression including osteorix, osteocalcin, and runx2 were increased after BMSC were treated with HAp-1 for 6 days. Although three kinds of HAps treatment for 9 days increased osteorix mRNA expression, osteocalcin, and runx2 mRNA expression levels were upregulated only by HAp-1. Similarly, only HAp-1 enhanced wedelolactone-induced osteocalcin, osteorix, and runx2 mRNA expression after 9 days treatment. Together, these results suggested that HAps with different sizes generated different effect on osteoblastogenesis. HAp-1 combined with wedelolacone can exert an enhanced effect on osteoblastogenesis, which has potential for treating osteoporosis. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 107A: 145–153, 2019.