Institute for Oral Science, Matsumoto Dental University, Nagano, 399-0781, Japan.
Department of Orthodontics, Matsumoto Dental University, Nagano, 399-0781, Japan.
Sci Rep. 2017 Jul 10;7(1):4928. doi: 10.1038/s41598-017-05401-1.
Bone marrow mesenchymal stem and progenitor cells (BM-MSPCs) maintain homeostasis of bone tissue by providing osteoblasts. Although several markers have been identified for labeling of MSPCs, these labeled cells still contain non-BM-MSPC populations. Studies have suggested that MSPCs are observed as leptin receptor (LepR)-positive cells, whereas osteoblasts can be classified as positive for Runx2, a master regulator for osteoblastogenesis. Here, we demonstrate, using Runx2-GFP reporter mice, that the LepR-labeled population contains Runx2-GFP sub-population, which possesses higher fibroblastic colony-forming units (CFUs) and mesensphere capacity, criteria for assessing stem cell activity, than the Runx2-GFP population. In response to parathyroid hormone (PTH), a bone anabolic hormone, LepRRunx2-GFP cells increase Runx2 expression and form multilayered structures near the bone surface. Subsequently, the multilayered cells express Osterix and Type I collagen α, resulting in generation of mature osteoblasts. Therefore, our results indicate that Runx2 is weakly expressed in the LepR population without osteoblastic commitment, and the LepRRunx2-GFP stromal cells sit atop the BM stromal hierarchy.
骨髓间充质干细胞和祖细胞（BM-MSPCs）通过提供成骨细胞来维持骨组织的稳态。尽管已经确定了几种标记物来标记 MSPCs，但这些标记的细胞仍然包含非 BM-MSPC 群体。研究表明，MSPCs 被观察为瘦素受体（LepR）阳性细胞，而成骨细胞可以被归类为 Runx2 阳性，Runx2 是成骨细胞发生的主要调节因子。在这里，我们使用 Runx2-GFP 报告小鼠证明，LepR 标记的群体包含 Runx2-GFP 亚群，该亚群具有更高的成纤维细胞集落形成单位（CFUs）和间质球能力，这是评估干细胞活性的标准，高于 Runx2-GFP 群体。对甲状旁腺激素（PTH），一种骨合成代谢激素，LepRRunx2-GFP 细胞增加 Runx2 表达并在骨表面附近形成多层结构。随后，多层细胞表达 Osterix 和 I 型胶原 α，导致成熟成骨细胞的生成。因此，我们的结果表明，Runx2 在没有成骨细胞承诺的情况下在 LepR 群体中弱表达，并且 LepRRunx2-GFP 基质细胞位于骨髓基质层次结构的顶部。
