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

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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5503992/
https://www.ncbi.nlm.nih.gov/pubmed/28694469
http://dx.doi.org/10.1038/s41598-017-05401-1
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author 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
author_facet 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
author_sort Yang, Mengyu
collection PubMed
description 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.
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spelling pubmed-55039922017-07-12 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 Sci Rep Article 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. Nature Publishing Group UK 2017-07-10 /pmc/articles/PMC5503992/ /pubmed/28694469 http://dx.doi.org/10.1038/s41598-017-05401-1 Text en © The Author(s) 2017 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
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
title 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_short 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
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5503992/
https://www.ncbi.nlm.nih.gov/pubmed/28694469
http://dx.doi.org/10.1038/s41598-017-05401-1
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