engleski

Acute hematopoietic stress in mice is followed by enhanced osteoclast maturation in the bone marrow microenvironment

Osteoclasts are components of HSC niches, but their role as contributors to the HSC homeostasis and release are still controversial. We aimed to investigate whether an acute blood loss of 10% of total blood content, and the consequent intense hematopoiesis would affect osteoclast differentiation and activity. Isolated peripheral blood (PBL), spleen, and bone marrow (BM) cells from bones of hind limbs were investigated for the presence of specific subpopulations of osteoclast precursors – B220-CD3-NK1.1-CD11b-/lowCD115+CD117+ cells in BM, and B220-CD3-NK1.1-Gr-1-CD11b+CD115+ cells in PBL and spleen, as well as the RANK+ cycle-arrested quiescent osteoclast precursors (QOPs). Expression of osteoclastogenesis-related genes: CD115, RANK, and cathepsin K, and the potential of BM cells to form osteoclast-like cells in vitro and their activity in vivo were also evaluated. We observed an increase in spleen cellularity and myelopoiesis during 1 week following blood loss, without any significant effects on BM cellularity or BM myeloid precursors including cells with high osteoclastogenic potential. However, at 1 week post-bleeding, hematopoiesis significantly promoted the expression of cathepsin K, IL-34, and BMP-6. QOPs increased significantly in spleen 2 days following bleeding, while osteoclast activity remained unchanged up to 2 weeks post-bleeding. Osteoclast- dependent B-cell differentiation was affected at the pre-B stage of maturation in BM, while the LSK population expanded in BM and spleen after 2 days post-bleeding. Our data demonstrate that an acute blood loss promotes differentiation and maturation of osteoclasts at 1 week, but does not enhance osteoresorption in vivo up to 2 weeks of the recovery period, and identifies osteoclast differentiation as a consequent and important event in establishing HSCs homeostasis following hematopoietic stress.

Hemorrhage; Hematopoiesis; Hematopoietic stem cells; Osteoblast; Osteoclast

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