Department of Medicine and Whitaker Cardiovascular Institute, Boston University School of Medicine, Boston, MA 02118, USA.
Departments of Biochemistry and Biology, Boston University School of Medicine, Boston, MA 02118, USA.
Cells. 2020 Apr 6;9(4):894. doi: 10.3390/cells9040894.
The biomechanical properties of the bone marrow microenvironment emerge from a combination of interactions between various extracellular matrix (ECM) structural proteins and soluble factors. Matrix stiffness directs stem cell fate, and both bone marrow stromal and hematopoietic cells respond to biophysical cues. Within the bone marrow, the megakaryoblasts and erythroblasts are thought to originate from a common progenitor, giving rise to fully mature magakaryocytes (the platelet precursors) and erythrocytes. Erythroid and megakaryocytic progenitors sense and respond to the ECM through cell surface adhesion receptors such as integrins and mechanosensitive ion channels. While hematopoietic stem progenitor cells remain quiescent on stiffer ECM substrates, the maturation of the erythroid and megakaryocytic lineages occurs on softer ECM substrates. This review surveys the major matrix structural proteins that contribute to the overall biomechanical tone of the bone marrow, as well as key integrins and mechanosensitive ion channels identified as ECM sensors in context of megakaryocytosis or erythropoiesis.
骨髓微环境的生物力学特性源于各种细胞外基质(ECM)结构蛋白和可溶性因子之间的组合相互作用。基质硬度决定了干细胞的命运,骨髓基质细胞和造血细胞都对生物物理线索做出反应。在骨髓中,巨核母细胞和红细胞被认为起源于一个共同的祖细胞,从而产生完全成熟的巨核细胞(血小板前体)和红细胞。红细胞和巨核细胞祖细胞通过细胞表面粘附受体(如整合素和机械敏感离子通道)感知和响应细胞外基质。虽然造血干细胞祖细胞在较硬的 ECM 基质上保持静止,但红细胞和巨核细胞谱系的成熟发生在较软的 ECM 基质上。这篇综述调查了主要的基质结构蛋白,这些蛋白有助于骨髓的整体生物力学特性,以及在巨核细胞生成或红细胞生成过程中被确定为 ECM 传感器的关键整合素和机械敏感离子通道。