Imbalanced Osteogenesis and Adipogenesis in Mice Deficient in the Chemokine Cxcl12/Sdf1 in the Bone Mesenchymal Stem/Progenitor Cells

ABSTRACT Bone and bone marrow serve as an imperative ecosystem to various types of cells participating in critical body functions. The chemokine Cxcl12, also known as stromal cell‐derived factor 1 (Sdf1), is one of the communication factors in the marrow microenvironment that regulates hematopoietic...

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Published inJournal of bone and mineral research Vol. 33; no. 4; pp. 679 - 690
Main Authors Tzeng, Yi‐Shiuan, Chung, Ni‐Chun, Chen, Yu‐Ren, Huang, Hsin‐Yi, Chuang, Wen‐Po, Lai, Dar‐Ming
Format Journal Article
LanguageEnglish
Published United States Oxford University Press 01.04.2018
Subjects
Adipocytes
Adipogenesis
Adipose tissue
Bone marrow
BONE‐FAT INTERACTIONS
Cancellous bone
Cell interactions
CELL/TISSUE SIGNALING–PARACRINE PATHWAYS
Chemokines
Clonal deletion
CXCL12
CXCL12 protein
CXCR4 protein
Gene deletion
GENETIC ANIMAL MODELS
Hematopoietic stem cells
Homeobox
Homeostasis
Mesenchyme
OSTEOBLAST
Osteoblasts
Osteogenesis
Osteoprogenitor cells
Progenitor cells
Rodents
SDF-1 protein
STROMAL/STEM CELLS
CELL/TISSUE SIGNALING-PARACRINE PATHWAYS
OSTEOBLAST
CXCL12
GENETIC ANIMAL MODELS
STROMAL/STEM CELLS
BONE-FAT INTERACTIONS
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Abstract ABSTRACT Bone and bone marrow serve as an imperative ecosystem to various types of cells participating in critical body functions. The chemokine Cxcl12, also known as stromal cell‐derived factor 1 (Sdf1), is one of the communication factors in the marrow microenvironment that regulates hematopoietic stem/progenitor cell homeostasis. However, the function of Cxcl12 in other bone marrow cells in vivo is yet to be discovered. Here we report a novel function of Cxcl12 in postnatal bone development and homeostasis. Targeted deletion of Cxcl12 in Paired related homeobox 1 (Prx1)‐expressing or osterix (Osx)‐expressing mesenchymal stem/progenitor cells (MSPCs), but not in mature osteoblasts, resulted in marrow adiposity and reduced trabecular bone content. In vivo lineage tracing analysis revealed biased differentiation of MSPCs toward adipocytes. In contrast, adult‐stage deletion of Cxcl12 in Osx‐expressing cells led to reduced bone content but not adiposity. Targeting the receptor Cxcr4 in the Prx1‐expressing cells also resulted in reduced trabecular bone content but not adiposity. Our study reveals a previously unidentified role of the MSPC‐secreting Cxcl12 that regulates its osteogenesis and adipogenesis through the cell‐autonomous and non‐autonomous mechanism, respectively; which could further influence the homeostatic control of the hematopoietic system. © 2017 American Society for Bone and Mineral Research
AbstractList Bone and bone marrow serve as an imperative ecosystem to various types of cells participating in critical body functions. The chemokine Cxcl12, also known as stromal cell‐derived factor 1 (Sdf1), is one of the communication factors in the marrow microenvironment that regulates hematopoietic stem/progenitor cell homeostasis. However, the function of Cxcl12 in other bone marrow cells in vivo is yet to be discovered. Here we report a novel function of Cxcl12 in postnatal bone development and homeostasis. Targeted deletion of Cxcl12 in Paired related homeobox 1 (Prx1)‐expressing or osterix (Osx)‐expressing mesenchymal stem/progenitor cells (MSPCs), but not in mature osteoblasts, resulted in marrow adiposity and reduced trabecular bone content. In vivo lineage tracing analysis revealed biased differentiation of MSPCs toward adipocytes. In contrast, adult‐stage deletion of Cxcl12 in Osx‐expressing cells led to reduced bone content but not adiposity. Targeting the receptor Cxcr4 in the Prx1‐expressing cells also resulted in reduced trabecular bone content but not adiposity. Our study reveals a previously unidentified role of the MSPC‐secreting Cxcl12 that regulates its osteogenesis and adipogenesis through the cell‐autonomous and non‐autonomous mechanism, respectively; which could further influence the homeostatic control of the hematopoietic system. © 2017 American Society for Bone and Mineral Research
Bone and bone marrow serve as an imperative ecosystem to various types of cells participating in critical body functions. The chemokine Cxcl12, also known as stromal cell-derived factor 1 (Sdf1), is one of the communication factors in the marrow microenvironment that regulates hematopoietic stem/progenitor cell homeostasis. However, the function of Cxcl12 in other bone marrow cells in vivo is yet to be discovered. Here we report a novel function of Cxcl12 in postnatal bone development and homeostasis. Targeted deletion of Cxcl12 in Paired related homeobox 1 (Prx1)-expressing or osterix (Osx)-expressing mesenchymal stem/progenitor cells (MSPCs), but not in mature osteoblasts, resulted in marrow adiposity and reduced trabecular bone content. In vivo lineage tracing analysis revealed biased differentiation of MSPCs toward adipocytes. In contrast, adult-stage deletion of Cxcl12 in Osx-expressing cells led to reduced bone content but not adiposity. Targeting the receptor Cxcr4 in the Prx1-expressing cells also resulted in reduced trabecular bone content but not adiposity. Our study reveals a previously unidentified role of the MSPC-secreting Cxcl12 that regulates its osteogenesis and adipogenesis through the cell-autonomous and non-autonomous mechanism, respectively; which could further influence the homeostatic control of the hematopoietic system. © 2017 American Society for Bone and Mineral Research.
ABSTRACT Bone and bone marrow serve as an imperative ecosystem to various types of cells participating in critical body functions. The chemokine Cxcl12, also known as stromal cell‐derived factor 1 (Sdf1), is one of the communication factors in the marrow microenvironment that regulates hematopoietic stem/progenitor cell homeostasis. However, the function of Cxcl12 in other bone marrow cells in vivo is yet to be discovered. Here we report a novel function of Cxcl12 in postnatal bone development and homeostasis. Targeted deletion of Cxcl12 in Paired related homeobox 1 (Prx1)‐expressing or osterix (Osx)‐expressing mesenchymal stem/progenitor cells (MSPCs), but not in mature osteoblasts, resulted in marrow adiposity and reduced trabecular bone content. In vivo lineage tracing analysis revealed biased differentiation of MSPCs toward adipocytes. In contrast, adult‐stage deletion of Cxcl12 in Osx‐expressing cells led to reduced bone content but not adiposity. Targeting the receptor Cxcr4 in the Prx1‐expressing cells also resulted in reduced trabecular bone content but not adiposity. Our study reveals a previously unidentified role of the MSPC‐secreting Cxcl12 that regulates its osteogenesis and adipogenesis through the cell‐autonomous and non‐autonomous mechanism, respectively; which could further influence the homeostatic control of the hematopoietic system. © 2017 American Society for Bone and Mineral Research
Bone and bone marrow serve as an imperative ecosystem to various types of cells participating in critical body functions. The chemokine Cxcl12, also known as stromal cell-derived factor 1 (Sdf1), is one of the communication factors in the marrow microenvironment that regulates hematopoietic stem/progenitor cell homeostasis. However, the function of Cxcl12 in other bone marrow cells in vivo is yet to be discovered. Here we report a novel function of Cxcl12 in postnatal bone development and homeostasis. Targeted deletion of Cxcl12 in Paired related homeobox 1 (Prx1)-expressing or osterix (Osx)-expressing mesenchymal stem/progenitor cells (MSPCs), but not in mature osteoblasts, resulted in marrow adiposity and reduced trabecular bone content. In vivo lineage tracing analysis revealed biased differentiation of MSPCs toward adipocytes. In contrast, adult-stage deletion of Cxcl12 in Osx-expressing cells led to reduced bone content but not adiposity. Targeting the receptor Cxcr4 in the Prx1-expressing cells also resulted in reduced trabecular bone content but not adiposity. Our study reveals a previously unidentified role of the MSPC-secreting Cxcl12 that regulates its osteogenesis and adipogenesis through the cell-autonomous and non-autonomous mechanism, respectively; which could further influence the homeostatic control of the hematopoietic system. © 2017 American Society for Bone and Mineral Research.Bone and bone marrow serve as an imperative ecosystem to various types of cells participating in critical body functions. The chemokine Cxcl12, also known as stromal cell-derived factor 1 (Sdf1), is one of the communication factors in the marrow microenvironment that regulates hematopoietic stem/progenitor cell homeostasis. However, the function of Cxcl12 in other bone marrow cells in vivo is yet to be discovered. Here we report a novel function of Cxcl12 in postnatal bone development and homeostasis. Targeted deletion of Cxcl12 in Paired related homeobox 1 (Prx1)-expressing or osterix (Osx)-expressing mesenchymal stem/progenitor cells (MSPCs), but not in mature osteoblasts, resulted in marrow adiposity and reduced trabecular bone content. In vivo lineage tracing analysis revealed biased differentiation of MSPCs toward adipocytes. In contrast, adult-stage deletion of Cxcl12 in Osx-expressing cells led to reduced bone content but not adiposity. Targeting the receptor Cxcr4 in the Prx1-expressing cells also resulted in reduced trabecular bone content but not adiposity. Our study reveals a previously unidentified role of the MSPC-secreting Cxcl12 that regulates its osteogenesis and adipogenesis through the cell-autonomous and non-autonomous mechanism, respectively; which could further influence the homeostatic control of the hematopoietic system. © 2017 American Society for Bone and Mineral Research.
Author Tzeng, Yi‐Shiuan
Chung, Ni‐Chun
Huang, Hsin‐Yi
Lai, Dar‐Ming
Chuang, Wen‐Po
Chen, Yu‐Ren
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Issue 4
Keywords CELL/TISSUE SIGNALING-PARACRINE PATHWAYS
OSTEOBLAST
CXCL12
GENETIC ANIMAL MODELS
STROMAL/STEM CELLS
BONE-FAT INTERACTIONS
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Snippet ABSTRACT Bone and bone marrow serve as an imperative ecosystem to various types of cells participating in critical body functions. The chemokine Cxcl12, also...
Bone and bone marrow serve as an imperative ecosystem to various types of cells participating in critical body functions. The chemokine Cxcl12, also known as...
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SubjectTerms Adipocytes
Adipogenesis
Adipose tissue
Bone marrow
BONE‐FAT INTERACTIONS
Cancellous bone
Cell interactions
CELL/TISSUE SIGNALING–PARACRINE PATHWAYS
Chemokines
Clonal deletion
CXCL12
CXCL12 protein
CXCR4 protein
Gene deletion
GENETIC ANIMAL MODELS
Hematopoietic stem cells
Homeobox
Homeostasis
Mesenchyme
OSTEOBLAST
Osteoblasts
Osteogenesis
Osteoprogenitor cells
Progenitor cells
Rodents
SDF-1 protein
STROMAL/STEM CELLS
Title Imbalanced Osteogenesis and Adipogenesis in Mice Deficient in the Chemokine Cxcl12/Sdf1 in the Bone Mesenchymal Stem/Progenitor Cells
URI https://onlinelibrary.wiley.com/doi/abs/10.1002%2Fjbmr.3340
https://www.ncbi.nlm.nih.gov/pubmed/29120093
https://www.proquest.com/docview/2023534394
https://www.proquest.com/docview/1962432777
Volume 33
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