Journal
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY
Volume 322, Issue 2, Pages C177-C184Publisher
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajpcell.00328.2021
Keywords
bone; megakaryocyte; osteoblast; osteoclast; osteosclerosis
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Funding
- Canadian Institutes for Health Research [CIHR PJT-152926]
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Multiple studies have shown reciprocal communications between bone marrow hematopoiesis and bone remodeling processes, with megakaryocytes playing a role in bone homeostasis. The effects of megakaryocytes on bone cells are influenced by the age and sex of animals, and they stimulate osteoblast proliferation while having variable effects on osteoclast proliferation and activity through soluble factors and direct cell-cell communications.
Over the years, numerous studies demonstrated reciprocal communications between processes of bone marrow hematopoiesis and bone remodeling. Megakaryocytes, rare bone marrow cells responsible for platelet production, were demonstrated to be involved in bone homeostasis. Myelofibrosis, characterized by an increase in pleomorphic megakaryocytes in the bone marrow, commonly leads to the development of osteosclerosis. In vivo, an increase in megakaryocyte number was shown to result in osteosclerosis in GATA-1(low), Nf-e2(-/-), TPOhigh, Mpl(f/f);PF4cre, Lnk(-/-), Mpig6b(-/-), Mpig6b(fl/fl);Gp1ba-Cr+/KI, and Pt-vWD mouse models. In vitro, megakaryocytes stimulate osteoblast proliferation and have variable effects on osteoclast proliferation and activity through soluble factors and direct cell-cell communications. Intriguingly, new studies revealed that the ability of megakaryocytes to communicate with bone cells is affected by the age and sex of animals. This mini-review summarizes changes seen in bone architecture and bone cell function in mouse models with an elevated number of megakaryocytes and the effects megakaryocytes have on osteoblasts and osteoclasts in vitro, and discusses potential molecular players that can mediate these effects.
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