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

• Published in: Journal 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
• Language: English
• 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
• ISSN: 0884-0431; 1523-4681; 1523-4681
• DOI: 10.1002/jbmr.3340

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