Receptor-interacting serine-threonine kinase 3 (RIPk3) is a key signaling molecule in the regulation of cell apoptosis and necroptosis, it plays an important role in the pathophysiological changes of many hematologic diseases. However, the regulatory role of RIPk3 in programmed cell death (PCD) is not fully known. In this study, bone marrow-specific RIPk3 gene knockout homozygotes (RIPk3-/- mice) were established by homologous recombination. The physiological index of peripheral blood, the morphology and structure of the bone marrow, the bone marrow nucleated cells (BMNCs), the hemopoietic stem cells (HSCs), interleukin-6 (IL-6) level and the colony formation capacity of bone marrow hematopoietic progenitor cells were compared between RIPk3-/- mice and wild-type mice. The results showed that, the cell death rate of BMNCs in RIPk3-/- mice was significantly higher than that in control mice, indicated that RIPk3 gene knockout may cause damage to bone marrow cells to some extent. However, the bone marrow had normal structure and morphology in the bone marrow-specific RIPk3-knockout mice, and there were not significantly different between the two mice in most of the blood physiological indicators, and colony yields of hemopoietic stem/progenitor cells. Further study found that the bone marrow IL-6 level of the RIPk3-/- mice increased significantly, besides, the number of BMNCs and HSCs in the bone marrow of the RIPk3-/- mice increased considerably as compared with the control mice. The findings implies that bone marrow RIPk3 gene knockout may lead to the increase of BMNCs cell death, however, increased secretion of hematopoietic cytokines such as IL-6 may promote the proliferation of hematopoietic stem/progenitor cells and thus maintain the stability of bone marrow hematopoiesis. This hypothesis and the detailed mechanisms remain to be further investigated.
Keywords: Bone marrow; RIPK3; gene knockout; hematopoiesis; mouse.
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