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

Mengyu Yang, Atsushi Arai, Nobuyuki Udagawa, Toru Hiraga, Zhao Lijuan, Susumu Ito, Toshihisa Komori, Takeshi Moriishi, Koichi Matsuo, Kouji Shimoda, Ali H. Zahalka, Yasuhiro Kobayashi, Naoyuki Takahashi, Toshihide Mizoguchi

Research output: Contribution to journalArticle

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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.

Original languageEnglish
Article number4928
JournalScientific Reports
Volume7
Issue number1
DOIs
Publication statusPublished - 2017 Dec 1

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Leptin Receptors
Mesenchymal Stromal Cells
Osteoblasts
Population
Bone and Bones
Stem Cells
Bone Marrow
Stromal Cells
Collagen Type I
Parathyroid Hormone
Homeostasis
Hormones

ASJC Scopus subject areas

  • General

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Osteogenic Factor Runx2 Marks a Subset of Leptin Receptor-Positive Cells that Sit Atop the Bone Marrow Stromal Cell Hierarchy. / Yang, Mengyu; Arai, Atsushi; Udagawa, Nobuyuki; Hiraga, Toru; Lijuan, Zhao; Ito, Susumu; Komori, Toshihisa; Moriishi, Takeshi; Matsuo, Koichi; Shimoda, Kouji; Zahalka, Ali H.; Kobayashi, Yasuhiro; Takahashi, Naoyuki; Mizoguchi, Toshihide.

In: Scientific Reports, Vol. 7, No. 1, 4928, 01.12.2017.

Research output: Contribution to journalArticle

Yang, M, Arai, A, Udagawa, N, Hiraga, T, Lijuan, Z, Ito, S, Komori, T, Moriishi, T, Matsuo, K, Shimoda, K, Zahalka, AH, Kobayashi, Y, Takahashi, N & Mizoguchi, T 2017, 'Osteogenic Factor Runx2 Marks a Subset of Leptin Receptor-Positive Cells that Sit Atop the Bone Marrow Stromal Cell Hierarchy', Scientific Reports, vol. 7, no. 1, 4928. https://doi.org/10.1038/s41598-017-05401-1
Yang, Mengyu ; Arai, Atsushi ; Udagawa, Nobuyuki ; Hiraga, Toru ; Lijuan, Zhao ; Ito, Susumu ; Komori, Toshihisa ; Moriishi, Takeshi ; Matsuo, Koichi ; Shimoda, Kouji ; Zahalka, Ali H. ; Kobayashi, Yasuhiro ; Takahashi, Naoyuki ; Mizoguchi, Toshihide. / Osteogenic Factor Runx2 Marks a Subset of Leptin Receptor-Positive Cells that Sit Atop the Bone Marrow Stromal Cell Hierarchy. In: Scientific Reports. 2017 ; Vol. 7, No. 1.
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AU - Hiraga, Toru

AU - Lijuan, Zhao

AU - Ito, Susumu

AU - Komori, Toshihisa

AU - Moriishi, Takeshi

AU - Matsuo, Koichi

AU - Shimoda, Kouji

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AB - 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.

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