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Megakaryocytes promote osteoclastogenesis in aging

Year: 2020
Type: article
Abstract: 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.
Source: Aging
DOI: 10.18632/aging.103595
Authors: Deepa Kanagasabapathy, Rachel J. Blosser, Kevin A. Maupin, Jung Min Hong, Marta Alvarez, Joydeep Ghosh, Safa F. Mohamad, Alexandra Aguilar-Perez, Edward F. Srour, Melissa A. Kacena, Angela Bruzzaniti
Language: English
Open Access status: green
Funders: National Institutes of Health, National Institute on Aging, National Cancer Institute, National Institute of Diabetes and Digestive and Kidney Diseases, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Center for Advancing Translational Sciences
Awards: Indiana Clinical and Translational Sciences Institute, A megakaryocyte/PGE2/osteoblast triad in the normal and aged niche, Osteomacs and megakaryocytes interact to regulate hematopoietic stem cell function, BD FACSAria System, Regulation of Osteoblast Function by Megakaryocytes: Key Signaling Proteins, Osteomacs and megakaryocytes interact to regulate hematopoietic stem cell function, Hematopoietic stem and progenitor cell regulation for enhanced clinical efficacy, Comprehensive Musculoskeletal Training Program, Indiana University Melvin and Bren Simon Comprehensive Cancer Center Support Grant
OpenAlex ID: W3042071790
FWCI: 0.649
Cites: 48
Cited by: 14
Related to: 10