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长期卸载后短期再加载可确保C57Bl/6N小鼠胫骨骨髓中基质细胞而非造血前体细胞活性的恢复。

Short-Term Reloading After Prolonged Unloading Ensures Restoration of Stromal but Not Hematopoietic Precursor Activity in Tibia Bone Marrow of C57Bl/6N Mice.

作者信息

Markina Elena A, Alekseeva Olga Y, Andreeva Elena R, Buravkova Ludmila B

机构信息

Cell Physiology Laboratory, Institute of Biomedical Problems, Russian Academy of Sciences, Moscow, Russian Federation.

出版信息

Stem Cells Dev. 2021 Dec 15;30(24):1228-1240. doi: 10.1089/scd.2021.0111. Epub 2021 Nov 30.

Abstract

Bone and muscle tissues are mostly susceptible to different kinds of hypodynamia, including real and simulated microgravity (sμg). To evaluate the effect of sμg on bone marrow (BM), male C57Bl/6N mice were divided into three groups: vivarium control (VC), 30-day hindlimb suspension (HS), and subsequent 12-h short-term support reloading (RL). The effects on BM total mononucleated cells (MNCs) as well as stromal and hematopoietic progenitors from murine tibia were studied. The number of BM MNCs, immunophenotype, proliferation, colony-forming units (CFUs), differentiation and secretory activity of hematopoietic and stromal BM cells were determined. HS led to a twofold decrease in MNCs, alteration of surface molecule expression profiles, suppression of proliferative activity of BM cells, and change of soluble mediators' levels. The stromal compartment was characterized by a decrease of CFU of fibroblasts and suppression of spontaneous osteo-commitment after HS. Among the hematopoietic precursors, a decrease in the total number of CFUs was found mainly at the expense of suppression of CFU-GM and CFU-GEMM. After RL, restoration of the stromal precursor's functional activity to control levels and overabundance of paracrine mediator's production were detected, whereas the complete recovery of hematopoietic precursor's activity did not occur. These data demonstrate the fast functional reaction of the stromal compartment on restoration of loading support.

摘要

骨骼和肌肉组织最易受到不同类型的动力不足影响,包括真实和模拟微重力(sμg)。为评估sμg对骨髓(BM)的影响,将雄性C57Bl/6N小鼠分为三组:饲养室对照(VC)组、30天的后肢悬吊(HS)组以及随后12小时的短期支持再负荷(RL)组。研究了对小鼠胫骨骨髓单个核细胞(MNCs)以及基质和造血祖细胞的影响。测定了骨髓MNCs的数量、免疫表型、增殖、集落形成单位(CFUs)、造血和基质骨髓细胞的分化及分泌活性。HS导致MNCs数量减少两倍、表面分子表达谱改变、骨髓细胞增殖活性受到抑制以及可溶性介质水平发生变化。基质区的特征是成纤维细胞CFU减少以及HS后自发骨定向分化受到抑制。在造血前体细胞中,CFUs总数减少主要是由于CFU-GM和CFU-GEMM受到抑制。RL后,检测到基质前体细胞的功能活性恢复到对照水平且旁分泌介质产生过多,而造血前体细胞的活性并未完全恢复。这些数据证明了基质区对负荷支持恢复的快速功能反应。

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