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

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 ob...

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Autores principales:	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
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Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/cadaaf04dcdd4fafb0cada7bb88b1263
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spelling	oai:doaj.org-article:cadaaf04dcdd4fafb0cada7bb88b12632021-12-02T12:32:36ZOsteogenic Factor Runx2 Marks a Subset of Leptin Receptor-Positive Cells that Sit Atop the Bone Marrow Stromal Cell Hierarchy10.1038/s41598-017-05401-12045-2322https://doaj.org/article/cadaaf04dcdd4fafb0cada7bb88b12632017-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-05401-1https://doaj.org/toc/2045-2322Abstract 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.Mengyu YangAtsushi AraiNobuyuki UdagawaToru HiragaZhao LijuanSusumu ItoToshihisa KomoriTakeshi MoriishiKoichi MatsuoKouji ShimodaAli H. ZahalkaYasuhiro KobayashiNaoyuki TakahashiToshihide MizoguchiNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-11 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q 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 Osteogenic Factor Runx2 Marks a Subset of Leptin Receptor-Positive Cells that Sit Atop the Bone Marrow Stromal Cell Hierarchy
description	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.
format	article
author	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
author_facet	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
author_sort	Mengyu Yang
title	Osteogenic Factor Runx2 Marks a Subset of Leptin Receptor-Positive Cells that Sit Atop the Bone Marrow Stromal Cell Hierarchy
title_short	Osteogenic Factor Runx2 Marks a Subset of Leptin Receptor-Positive Cells that Sit Atop the Bone Marrow Stromal Cell Hierarchy
title_full	Osteogenic Factor Runx2 Marks a Subset of Leptin Receptor-Positive Cells that Sit Atop the Bone Marrow Stromal Cell Hierarchy
title_fullStr	Osteogenic Factor Runx2 Marks a Subset of Leptin Receptor-Positive Cells that Sit Atop the Bone Marrow Stromal Cell Hierarchy
title_full_unstemmed	Osteogenic Factor Runx2 Marks a Subset of Leptin Receptor-Positive Cells that Sit Atop the Bone Marrow Stromal Cell Hierarchy
title_sort	osteogenic factor runx2 marks a subset of leptin receptor-positive cells that sit atop the bone marrow stromal cell hierarchy
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/cadaaf04dcdd4fafb0cada7bb88b1263
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Osteogenic Factor Runx2 Marks a Subset of Leptin Receptor-Positive Cells that Sit Atop the Bone Marrow Stromal Cell Hierarchy

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