Research Center for Biomineralization Disorders, School of Dentistry, Chonnam National University, Gwangju, Republic of Korea.
Department of Pharmacology and Dental Therapeutics, School of Dentistry, Chonnam National University, Gwangju, Republic of Korea.
Exp Mol Med. 2018 Nov 5;50(11):1-16. doi: 10.1038/s12276-018-0170-6.
Supplementation of mesenchymal stem cells (MSCs) at sites of bone resorption is required for bone homeostasis because of the non-proliferation and short lifespan properties of the osteoblasts. Calcium ions (Ca) are released from the bone surfaces during osteoclast-mediated bone resorption. However, how elevated extracellular Ca concentrations would alter MSCs behavior in the proximal sites of bone resorption is largely unknown. In this study, we investigated the effect of extracellular Ca on MSCs phenotype depending on Ca concentrations. We found that the elevated extracellular Ca promoted cell proliferation and matrix mineralization of MSCs. In addition, MSCs induced the expression and secretion of osteopontin (OPN), which enhanced MSCs migration under the elevated extracellular Ca conditions. We developed in vitro osteoclast-mediated bone resorption conditions using mouse calvaria bone slices and demonstrated Ca is released from bone resorption surfaces. We also showed that the MSCs phenotype, including cell proliferation and migration, changed when the cells were treated with a bone resorption-conditioned medium. These findings suggest that the dynamic changes in Ca concentrations in the microenvironments of bone remodeling surfaces modulate MSCs phenotype and thereby contribute to bone regeneration.
补充骨髓间充质干细胞（MSCs）是维持骨稳态所必需的，因为成骨细胞具有非增殖和寿命短的特性。破骨细胞介导的骨吸收会导致骨表面释放钙离子（Ca）。然而，升高的细胞外 Ca 浓度如何改变骨吸收近侧部位的 MSCs 行为在很大程度上尚不清楚。在这项研究中，我们研究了细胞外 Ca 浓度对 MSCs 表型的影响。我们发现，升高的细胞外 Ca 促进了 MSCs 的增殖和基质矿化。此外，MSCs 诱导骨桥蛋白（OPN）的表达和分泌，这增强了 MSCs 在升高的细胞外 Ca 条件下的迁移。我们使用小鼠颅骨骨片开发了体外破骨细胞介导的骨吸收条件，并证明了 Ca 从骨吸收表面释放出来。我们还表明，当用骨吸收条件培养基处理细胞时，MSCs 的表型，包括细胞增殖和迁移，会发生变化。这些发现表明，骨重塑表面微环境中 Ca 浓度的动态变化调节 MSCs 表型，从而有助于骨再生。
