Article Cite This: ACS Biomater. Sci. Eng. 2019, 5, 3483−3498
pubs.acs.org/journal/abseba
Bone Mineral Crystallinity Governs the Orchestration of Ossification and Resorption during Bone Remodeling Vuk Uskokovic,́ *,†,‡,§ Ivona Jankovic-́ Č astvan,⊥ and Victoria M. Wu‡
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Department of Mechanical and Aerospace Engineering, University of California, Irvine, Engineering Gateway 4200, Irvine, California 92697, United States ‡ Department of Bioengineering, University of Illinois, 851 South Morgan Street, Chicago, Illinois 60607-7052, United States § Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, 1600 Fourth Street, San Francisco, California 94158, United States ⊥ Faculty of Technology and Metallurgy, University of Belgrade, Karnegijeva 4, Belgrade 11000, Serbia ABSTRACT: The circularly causal orchestration of bone production and destruction is a part of the standard model of bone remodeling, but the crystallinity of the bone mineral, which naturally alternates during this process, has not had a steady place in it. Here we show that osteoclasts and osteoblasts, the cells resorbing and building bone, respectively, can sense the crystallinity of the bone mineral and adjust their activity thereto. Specifically, osteoblastic MC3T3-E1 cells secreted mineral nodules more copiously when they were brought into contact with amorphous calcium phosphate (ACP) nanoparticles than when they were challenged with their crystalline, hydroxyapatite (HAp) analogues. Moreover, the gene expressions of osteogenic markers BGLAP, ALP, BSP-1, and RUNX2 in MC3T3-E1 cells were higher in the presence of ACP than in the presence of HAp. At the same time, the dental pulp stem cells differentiated into an osteoblastic phenotype to a degree that was inversely proportional to the amount and the crystallinity of the mineral added to their cultures. In contrast, the resorption of HAp nanoparticles was more intense than the resorption of ACP, as concluded by the greater retention of the latter particles inside the osteoclastic RAW264.7 cells after 10 days of incubation and also by the time-dependent free Ca2+ concentration measurements in the cell culture media at early incubation time points (
