低氧缺氧和后肢悬吊对小鼠骨骼稳态和造血的单独和联合影响

Marjorie Durand, J. Collombet, S. Frasca, Véronique Sarilar, J. Lataillade, M. Le Bousse-Kerdilès, X. Holy
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引用次数: 6

摘要

目的骨髓对机体应激的反应是通过协调造血干/祖细胞(HSPCs)和间充质基质细胞(MSC)之间的相互作用而产生的。调节这一过程的细胞因子和分子因子都不完全清楚,尤其是因为这种机制可能因压力类型而异。在此,我们探索了骨髓间充质干细胞和热休克蛋白在单独或联合应用造血应激或机械应激的小鼠中的分化和命运。方法对小鼠进行4天的低压缺氧(造血激发)和/或7天的后肢悬吊(基质激发),然后处死以采集血液和骨骼。使用血液学测量、集落形成单位测定、骨组织形态计量学和基于阵列的多重ELISA分析,我们评估了挑战对MSC和HSPC动员、分化(成骨细胞、破骨细胞和成熟血细胞)和命运的影响。结果我们发现缺氧导致HSPC动员,骨形成和骨吸收之间的不平衡是这种动员的原因。虽然悬浮液也与骨形成和骨吸收之间的不平衡有关,但它不会诱导HSPC动员。然后,我们通过将小鼠的造血和基质攻击结合起来,揭示了细胞间的相互作用。我们发现缺氧驱动的HSPC动员是由悬浮液调节的。此外,当在缺氧环境中使用时,悬浮液可以抵消骨骼失衡。我们确定基质细胞衍生因子MIP-1α、HGF和SDF-1是维持后肢悬吊和低压缺氧之间相互作用的有效分子关键因素。结论总之,我们的数据强调了将不同类型的应激结合起来以更好地理解MSCs和HSPCs之间的相互作用的好处。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Separate and combined effects of hypobaric hypoxia and hindlimb suspension on skeletal homeostasis and hematopoiesis in mice
Purpose Bone marrow response to an organismal stress is made by orchestrating the interplay between hematopoietic stem/progenitor cells (HSPCs) and mesenchymal stromal cells (MSCs). Neither the cellular nor the molecular factors that regulate this process are fully understood, especially since this mechanism probably varies depending on the type of stress. Herein, we explored the differentiation and fate of MSCs and HSPCs in mice challenged with a hematopoietic stress or a mechanical stress applied separately or in combination. Methods Mice were subjected to 4 days of hypobaric hypoxia (hematopoietic challenge) and/or 7 days of hindlimb suspension (stromal challenge) and then sacrificed for blood and bone collection. Using hematological measurements, colony-forming unit assays, bone histomorphometry and array-based multiplex ELISA analysis, we evaluated challenge influences on both MSC and HSPC mobilization, differentiation (osteoblasts, osteoclasts, and mature blood cells) and fate. Results We found that hypoxia leads to HSPC mobilization and that an imbalance between bone formation and bone resorption accounts for this mobilization. Whilst suspension is also associated with an imbalance between bone formation and bone resorption, it does not induce HSPC mobilization. Then, we revealed cellular interactions by combining hematopoietic and stromal challenges together in mice. We showed that the hypoxia-driven HSPC mobilization is moderated by suspension. Moreover, when applied in a hypoxic environment, suspension offsets bone imbalance. We identified stroma cell-derived factors MIP-1α, HGF and SDF-1 as potent molecular key players sustaining interactions between hindlimb suspension and hypobaric hypoxia. Conclusion Taken together, our data highlight the benefit of combining different types of stress to better understand the interplay between MSCs and HSPCs.
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