CXCR4+CD45− Cells are Niche Forming for Osteoclastogenesis via the SDF-1, CXCL7, and CX3CL1 Signaling Pathways in Bone Marrow
| Autor: | Takeo Sekiya, Hiroki Kakita, Yuko Waguri-Nagaya, Yoh Goto, Ken Miyazawa, Kiyofumi Asai, Mineyoshi Aoyama, Shigemi Goto |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
medicine.medical_specialty Chemokine biology Cell Biology Bone resorption Cell biology 03 medical and health sciences 030104 developmental biology 0302 clinical medicine Endocrinology medicine.anatomical_structure RANKL Osteoclast 030220 oncology & carcinogenesis Internal medicine CXCL7 biology.protein medicine Molecular Medicine Stromal cell-derived factor 1 Bone marrow Stem cell Developmental Biology |
| Zdroj: | Stem Cells. 34:2733-2743 |
| ISSN: | 1549-4918 1066-5099 |
| DOI: | 10.1002/stem.2440 |
| Popis: | Bone homeostasis comprises the balance between bone-forming osteoblasts and bone-resorbing osteoclasts (OCs), with an acceleration of osteoclastic bone resorption leading to osteoporosis. OCs can be generated from bone marrow cells (BMCs) under the tightly regulated local bone environment. However, it remained difficult to identify the critical cells responsible for providing an osteoclastogenesis niche. In this study, we used a fluorescence-activated cell sorting technique to determine the cell populations important for forming an appropriate microenvironment for osteoclastogenesis and to verify the associated interactions between osteoclast precursor cells and non-OCs. We isolated and removed a small cell population specific for osteoclastogenesis (CXCR4+ CD45−) from mouse BMCs and cultured the remaining cells with receptor activator of nuclear factor-kappa B ligand (RANKL) and macrophage-colony stimulating factor. The resulting cultures showed significantly less large osteoclast formation. Quantitative RT-PCR analysis revealed that these CXCR4+ CD45− cells expressed low levels of RANK and RANKL, but high levels of critical chemokines including stromal cell derived factor 1 (SDF-1), chemokine (C-X-C motif) ligand 7 (CXCL7), and chemokine (C-X3-C motif) ligand 1 (CX3CL1). Furthermore, an SDF-1-specific antibody strongly suppressed OC formation in RAW264.7 cells and antibodies against SDF-1, CXCL7, and CX3CL1 suppressed OC formation in BMCs. These results suggest that isolated CXCR4+ CD45− cells support an appropriate microenvironment for osteoclastogenesis with a direct effect on the cells expressing SDF-1, CXCL7, and CX3CL1 receptors. The regulation of CXCR4+ CD45− cell function might therefore inform therapeutic strategies for diseases involving loss of bone homeostasis. |
| Databáze: | OpenAIRE |
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