Open AccessOsteogenic Factor Runx2 Marks a Subset of Leptin Receptor-Positive Cells that Sit Atop the Bone Marrow Stromal Cell Hierarchy
Author(s) -
Mengyu Yang,
Atsushi Arai,
Nobuyuki Udagawa,
Toru Hiraga,
Lijuan Zhao,
Susumu Ito,
Toshihisa Komori,
Takeshi Moriishi,
Koichi Matsuo,
Kouji Shimoda,
Ali H. Zahalka,
Yasuhiro Kobayashi,
Naoyuki Takahashi,
Takahiro Mizoguchi
Publication year - 2017
Publication title -
scientific reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.24
H-Index - 213
ISSN - 2045-2322
DOI - 10.1038/s41598-017-05401-1
Subject(s) - stromal cell , runx2 , progenitor cell , population , bone marrow , parathyroid hormone , leptin receptor , stem cell , endocrinology , leptin , mesenchymal stem cell , microbiology and biotechnology , medicine , biology , chemistry , osteoblast , biochemistry , calcium , in vitro , obesity , environmental health
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 low 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-GFP low 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-GFP low stromal cells sit atop the BM stromal hierarchy.