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Matrix-embedded osteocytes regulate mobilization of hematopoietic stem/progenitor cells
Noboru Asada1, Yoshio Katayama, Mari Sato
1Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama 700-8558, Japan.
Cell Stem Cell
|June 11, 2013
Summary
Osteocytes, bone cells, regulate hematopoietic stem cell egress. Granulocyte colony-stimulating factor (G-CSF) mobilizes these cells by altering osteocyte networks, revealing a role for bone in blood cell production.
Area of Science:
- Bone Biology
- Hematopoiesis
- Cellular Regulation
Background:
- The bone marrow (BM) niche contains diverse cells controlling hematopoietic stem/progenitor cell (HSPC) circulation.
- Osteocytes, the most abundant cells in mature bone, have emerged as potential regulators of HSPC egress.
Purpose of the Study:
- To investigate the role of osteocytes in regulating hematopoietic stem/progenitor cell (HSPC) mobilization from the bone marrow.
- To elucidate the mechanism by which osteocytes influence HSPC egress in response to G-CSF.
Main Methods:
- Utilized mouse models with targeted osteocyte ablation or disrupted osteocyte networks.
- Administered G-CSF to induce HSPC mobilization and analyzed changes in osteocyte morphology and gene expression.
- Investigated the role of the sympathetic nervous system by examining osteocyte response and using surgical sympathectomy.
Main Results:
- Osteocytes rapidly alter morphology and gene expression upon G-CSF administration, preceding osteoblast changes.
- Osteocyte-specific disruption prevents HSPC mobilization in response to G-CSF.
- Osteocytes express the β2-adrenergic receptor, and sympathectomy blocks the G-CSF-induced response, implicating the sympathetic nervous system.
Conclusions:
- Osteocytes are critical regulators of hematopoietic stem/progenitor cell (HSPC) egress from the bone marrow.
- The bone marrow-bone niche interface is internally regulated by osteocytes within the bone matrix.
- Skeletal tissues play a significant physiological role in hematopoietic regulation.
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