Megakaryocyte-bone cell interactions: lessons from mouse models of experimental myelofibrosis and related disorders.
Mariya StavnichukSvetlana V KomarovaPublished in: American journal of physiology. Cell physiology (2021)
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 -/- , TPO high , 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.
Keyphrases
- bone marrow
- bone mineral density
- bone loss
- mouse model
- bone regeneration
- single cell
- signaling pathway
- soft tissue
- induced apoptosis
- mesenchymal stem cells
- cell therapy
- cell cycle arrest
- postmenopausal women
- oxidative stress
- transcription factor
- body composition
- risk assessment
- cell death
- pi k akt
- neoadjuvant chemotherapy
- endoplasmic reticulum stress
- inflammatory response
- rectal cancer
- nuclear factor
- locally advanced