Format

Send to

Choose Destination
Sci Rep. 2017 Jul 10;7(1):4928. doi: 10.1038/s41598-017-05401-1.

Osteogenic Factor Runx2 Marks a Subset of Leptin Receptor-Positive Cells that Sit Atop the Bone Marrow Stromal Cell Hierarchy.

Author information

1
Institute for Oral Science, Matsumoto Dental University, Nagano, 399-0781, Japan.
2
Department of Orthodontics, Matsumoto Dental University, Nagano, 399-0781, Japan.
3
Department of Oral Biochemistry, Matsumoto Dental University, Nagano, 399-0781, Japan.
4
Department of Histology and Cell Biology, Matsumoto Dental University, Nagano, 399-0781, Japan.
5
Division of Instrumental Analysis, Research Center for Human and Environmental Sciences, Shinshu University, Nagano, 390-8621, Japan.
6
Department of Cell Biology, Unit of Basic Sciences, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, 852-8588, Japan.
7
Laboratory of Cell and Tissue Biology, Keio University School of Medicine, Tokyo, 160-8582, Japan.
8
Laboratory Animal Center, Keio University School of Medicine, Tokyo, 160-8582, Japan.
9
Ruth L. and David S. Gottesman Institute for Stem Cell and Regenerative Medicine Research, Albert Einstein College of Medicine, Bronx, NY, 10461, USA.
10
Department of Cell Biology, Albert Einstein College of Medicine, Bronx, NY, 10461, USA.
11
Institute for Oral Science, Matsumoto Dental University, Nagano, 399-0781, Japan. toshim@po.mdu.ac.jp.

Abstract

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-GFPlow 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, LepR+Runx2-GFPlow 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 LepR+Runx2-GFPlow stromal cells sit atop the BM stromal hierarchy.

Supplemental Content

Full text links

Icon for Nature Publishing Group Icon for PubMed Central
Loading ...
Support Center