@article{
author = "Uskoković, Vuk and Janković-Častvan, Ivona and Wu, Victoria M.",
year = "2019",
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 ( lt 1 week), prior to the spontaneous crystallization of the amorphous phase. A detailed morphological, compositional, and microstructural characterization of ACP and HAp is provided too, and it is shown that although ACP transforms to HAp in the cell culture media, some microstructural properties are retained in the powder following this transformation, influencing the resorption rate. On the basis of these findings, a model of bone remodeling at the level of individual biogenic apatite nanoparticles was proposed, taking into account the effects of hydration and lattice strain. According to this model, apatite is a "living" mineral, undergoing fluctuations in crystallinity within a closed ossifying/resorptive feedback loop in a way that buffers against potential runaway effects. A finite degree of amorphousness of every apatite crystal in bone is seen as a vital prerequisite for a healthy, dynamic bone remodeling process, and the best bone mineral, from this standpoint, is the living mineral, the one undergoing a constant process of structural change in response to biochemical stimuli thanks to its partially amorphous microstructure and unique interfacial dynamics.",
publisher = "Amer Chemical Soc, Washington",
journal = "ACS Biomaterials Science & Engineering",
title = "Bone Mineral Crystallinity Governs the Orchestration of Ossification and Resorption during Bone Remodeling",
pages = "3498-3483",
number = "7",
volume = "5",
doi = "10.1021/acsbiomaterials.9b00255"
}
