Osteocyte regulation of bone and blood.

Osteocyte regulation of bone and blood.
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DOI:
10.1016/j.bone.2018.02.012
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发表时间:
2019-03
期刊:
影响因子:
4.1
通讯作者:
Krause DS
Krause DS
中科院分区:
医学2区
文献类型:
--
作者:
Divieti Pajevic P;Krause DS

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在过去的十年里,人们对基质嵌入骨细胞的功能和生物学重新产生了兴趣,这些细胞已成为骨稳态的主要调节因子。它们分泌两种非常强大的蛋白质:硬化素(一种 Wnt 抑制剂,可抑制骨形成)和 NF-kB 配体受体激活剂(RANKL),一种破骨细胞生成所需的细胞因子。针对这些蛋白质的中和抗体目前用于治疗骨质疏松症。然而,最近的研究将骨细胞的另一个功能归结为:直接或通过分泌因子控制造血和 HSPC 生态位。在缺乏骨细胞的情况下,HSC 动员和异常淋巴细胞生成会增加,而在这些细胞中缺乏 Gsα 信号传导的情况下,骨髓细胞会增加。骨细胞究竟如何控制造血或 HSPC 生态位尚不完全清楚。在这篇综述中,我们总结了骨细胞在骨骼中的作用,然后分析了这些细胞对造血的影响。进一步讨论了未来的方向和当前知识的差距。
This past decade has witnessed a renewed interest in the function and biology of matrix-embedded osteocytes and these cells have emerged as master regulators of bone homeostasis. They secrete two very powerful proteins, sclerostin, a Wnt-inhibitor, that suppresses bone formation, and receptor-activator of NF-kB ligand (RANKL), a cytokine required for osteoclastogenesis. Neutralizing antibodies against these proteins are currently used for the treatment of osteoporosis. Recent studies however, ascribed yet another function to osteocytes: the control of hematopoiesis and the HSPC niche, directly and through secreted factors. In the absence of osteocytes there is an increase in HSC mobilization and abnormal lymphopoiesis whereas in the absence of Gsα signaling in these cells there is an increase of myeloid cells. How exactly osteocytes control hematopoiesis or the HSPC niche is still not completely understood. In this review we summarize the actions of osteocytes in bone and then analyze the effects of these cells on hematopoiesis. Future directions and gaps in current knowledge are further discussed.
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