Irradiation-induced secretion of BMP4 by marrow cells causes marrow adipogenesis post-myelosuppression
| Autor: | Manmohan S. Bajaj, Vaijayanti Kale, Rohan S. Kulkarni, Lalita Limaye, Suprita S. Ghode |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Simvastatin Bone marrow cells PPAR-γ medicine.medical_specialty Stromal cell T-Lymphocytes BMP4 Bone Morphogenetic Protein 4 Biology Mice 03 medical and health sciences chemistry.chemical_compound Marrow adipogenesis Internal medicine Adipocyte Adipocytes medicine Animals Medicine(all) Adipogenesis Regeneration (biology) Cell Biology General Medicine Mice Inbred C57BL PPAR gamma Haematopoiesis 030104 developmental biology Endocrinology medicine.anatomical_structure chemistry Hematopoietic recovery Cancer research Irradiation Bone marrow Stromal Cells Stem cell Secretory Rate Whole-Body Irradiation Developmental Biology medicine.drug |
| Zdroj: | Stem Cell Research. 17:646-653 |
| ISSN: | 1873-5061 |
| DOI: | 10.1016/j.scr.2016.11.015 |
| Popis: | Pre-transplant myeloablation is associated with marrow adipogenesis, resulting in delayed engraftment of hematopoietic stem cells (HSCs). This is strongly undesirable, especially when the donor HSCs are fewer in numbers or have compromised functionality. The molecular mechanisms behind irradiation-induced marrow adipogenesis have not been extensively investigated. Here we show that bone marrow (BM) cells, especially T-cells and stromal cells, express and secrete copious amounts of BMP4 in response to irradiation, which causes the bone marrow stromal cells to commit to adipocyte lineage, thereby contributing to an increase in bone marrow adipogenesis. We further demonstrate that Simvastatin inhibits the BMP4-mediated adipogenic commitment of marrow stromal cells by inhibiting Ppar-γ expression. Importantly, Simvastatin does not prevent BMP4 secretion by the BM cells, and thus does not interfere with its salutary role in post-transplant hematopoietic regeneration. Our data identify previously unknown mechanisms operative in marrow adipogenesis post-myeloablation. They also reveal the molecular mechanisms behind the advantage of using Simvastatin as a niche-targeting agent to improve HSC engraftment. |
| Databáze: | OpenAIRE |
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