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

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.

Keywords: Bone mass; Hematopoiesis; Megakaryocyte; Osteoblast; Osteoclast.

Figure 1.. Key cell types in the bone marrow and how they change with age.

MKs and HSCs reside in the bone marrow while mature OBs and OCs reside on endosteal surfaces. MK and OC numbers increase with aging while OB number decreases. The distance between MKs and HSCs also increases with age.

Figure 2.

MK secreted cytokines, growth factors, and their target cells in the bone microenvironment.