Megakaryocytes promote osteoclastogenesis in aging
| Autor: | Alexandra Aguilar-Perez, Joydeep Ghosh, Safa F. Mohamad, Kevin A. Maupin, Marta B. Alvarez, Angela Bruzzaniti, Jung Min Hong, Edward F. Srour, Deepa Kanagasabapathy, Rachel J. Blosser, Melissa A. Kacena |
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| Rok vydání: | 2020 |
| Předmět: |
Aging
medicine.medical_specialty medicine.drug_class Bone resorption megakaryocyte Mice Sex Factors Megakaryocyte Bone Marrow Osteogenesis Osteoclast Internal medicine medicine Animals Bone Resorption Receptor Thrombopoietin Cell Proliferation biology Chemistry RANK Ligand Age Factors Cell Differentiation Estrogens Cell Biology Endocrinology medicine.anatomical_structure Estrogen RANKL osteoclast biology.protein Bone marrow bone marrow macrophage Megakaryocytes Receptors Thrombopoietin Research Paper Signal Transduction |
| Zdroj: | Aging (Albany NY) |
| ISSN: | 1945-4589 |
| Popis: | Megakaryocytes (MKs) support bone formation by stimulating osteoblasts (OBs) and inhibiting osteoclasts (OCs). Aging results in higher bone resorption, leading to bone loss. Whereas previous studies showed the effects of aging on MK-mediated bone formation, the effects of aging on MK-mediated OC formation is poorly understood. Here we examined the effect of thrombopoietin (TPO) and MK-derived conditioned media (CM) from young (3-4 months) and aged (22-25 months) mice on OC precursors. Our findings showed that aging significantly increased OC formation in vitro. Moreover, the expression of the TPO receptor, Mpl, and circulating TPO levels were elevated in the bone marrow cavity. We previously showed that MKs from young mice secrete factors that inhibit OC differentiation. However, rather than inhibiting OC development, we found that MKs from aged mice promote OC formation. Interestingly, these age-related changes in MK functionality were only observed using female MKs, potentially implicating the sex steroid, estrogen, in signaling. Further, RANKL expression was highly elevated in aged MKs suggesting MK-derived RANKL signaling may promote osteoclastogenesis in aging. Taken together, these data suggest that modulation in TPO-Mpl expression in bone marrow and age-related changes in the MK secretome promote osteoclastogenesis to impact skeletal aging. |
| Databáze: | OpenAIRE |
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