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Megakaryocyte Secreted Factors Regulate Bone Marrow Niche Cells During Skeletal Homeostasis, Aging, and Disease

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Abstract

The bone marrow microenvironment contains a diverse array of cell types under extensive regulatory control and provides for a novel and complex mechanism for bone regulation. Megakaryocytes (MKs) are one such cell type that potentially acts as a master regulator of the bone marrow microenvironment due to its effects on hematopoiesis, osteoblastogenesis, and osteoclastogenesis. While several of these processes are induced/inhibited through MK secreted factors, others are primarily regulated by direct cell–cell contact. Notably, the regulatory effects that MKs exert on these different cell populations has been found to change with aging and disease states. Overall, MKs are a critical component of the bone marrow that should be considered when examining regulation of the skeletal microenvironment. An increased understanding of the role of MKs in these physiological processes may provide insight into novel therapies that can be used to target specific pathways important in hematopoietic and skeletal disorders.

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Abbreviations

MK:

Megakaryocyte

OC:

Osteoclast

OB:

Osteoblast

HSC:

Hematopoietic stem cell

MSC:

Mesenchymal stem cell

BMM:

Bone marrow macrophage

TPO:

Thrombopoietin

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Acknowledgements

Figures were created using BioRender.com. This work was completed in part by funding from the Cooperative Center of Excellence in Hematology (CCEH) Indianapolis-Indiana University School of Medicine to AB and MAK. This work was supported in part with funding, resources, and the use of facilities at the School of Medicine and the School of Dentistry at Indiana University and the Richard L. Roudebush VA Medical Center, Indianapolis, IN.

Funding

NIH-NIAMS AR080076, Angela Bruzzaniti; NIH DK108342, DK118782/AG082275, AG060621, U.S. Department of Veterans Affairs I01RX003552, 1I01BX003751, Melissa A. Kacena.

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Author notes

  1. Sonali J. Karnik and Murad K. Nazzal have contributed equally to this work.

Authors and Affiliations

  1. Department of Orthopaedic Surgery, Indiana University School of Medicine, Indianapolis, IN, USA

    Sonali J. Karnik, Murad K. Nazzal & Melissa A. Kacena

  2. Richard L. Roudebush VA Medical Center, Indianapolis, IN, USA

    Melissa A. Kacena

  3. Department of Biomedical Sciences and Comprehensive Care, Indiana University School of Dentistry, Indianapolis, IN, USA

    Angela Bruzzaniti

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Contributions

AB and MAK conceptualized and designed the review article. Together SJK and MKN wrote the first draft of the manuscript. All authors completed literature searches, revised the manuscript critically for important intellectual content, take responsibility for all aspects of the work, and approve of the final version of the manuscript. AB are jointly responsible for the overall contents of the manuscript.

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Correspondence to Melissa A. Kacena or Angela Bruzzaniti.

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Sonali J. Karnik, Murad K. Nazzal, Melissa A. Kacena, and Angela Bruzzaniti declare that they have no competing interests that are relevant to the content of this article.

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Karnik, S.J., Nazzal, M.K., Kacena, M.A. et al. Megakaryocyte Secreted Factors Regulate Bone Marrow Niche Cells During Skeletal Homeostasis, Aging, and Disease. Calcif Tissue Int 113, 83–95 (2023). https://doi.org/10.1007/s00223-023-01095-y

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