Id1 represses osteoclast-dependent transcription and affects bone formation and hematopoiesis.
Id1 represses osteoclast-dependent transcription and affects bone formation and hematopoiesis.
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DOI：
10.1371/journal.pone.0007955
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发表时间：
2009-11-24
期刊：
影响因子：
3.7
通讯作者：
Lyden D
中科院分区：
文献类型：
--
作者：
Chan AS;Jensen KK;Skokos D;Doty S;Lederman HK;Kaplan RN;Rafii S;Rivella S;Lyden D
骨-骨髓界面是骨髓微环境的一个区域，其中骨重塑细胞、成骨细胞和破骨细胞以及造血细胞在解剖学上并置。这些细胞的紧密接近自然表明它们彼此相互作用，但这些相互作用才刚刚开始被表征。使用 Id1−/− 小鼠模型来评估 Id1 在骨髓微环境中的作用。微型计算机断层扫描和骨折测试表明，Id1−/− 小鼠骨量减少，骨脆性增加，与骨质疏松表型一致。破骨细胞生成和凹坑形成测定表明，Id1 的缺失增加了破骨细胞的分化和吸收活性，无论是在体内还是体外，这表明 Id1 作为破骨细胞分化的负调节因子具有细胞自主作用。通过流式细胞术对 Id1−/− 小鼠的造血室进行检查，结果显示骨髓分化有所增加。此外，我们发现 Id1−/− 骨髓微环境中破骨细胞基因 TRAP、Oscar 和 CTSK 的表达增加。最后，将野生型骨髓移植到 Id1−/− 小鼠中抑制了 TRAP、Oscar 和 CTSK 的表达和活性，并挽救了这些小鼠的造血和骨表型。总之，我们证明了 Id1−/− 小鼠的骨质疏松表型以及 Id1 破骨细胞相关基因转录控制的机制。我们的结果确定 Id1 是负责骨和骨髓造血细胞之间动态串扰的主要参与者。
The bone-bone marrow interface is an area of the bone marrow microenvironment in which both bone remodeling cells, osteoblasts and osteoclasts, and hematopoietic cells are anatomically juxtaposed. The close proximity of these cells naturally suggests that they interact with one another, but these interactions are just beginning to be characterized. An Id1−/− mouse model was used to assess the role of Id1 in the bone marrow microenvironment. Micro-computed tomography and fracture tests showed that Id1−/− mice have reduced bone mass and increased bone fragility, consistent with an osteoporotic phenotype. Osteoclastogenesis and pit formation assays revealed that loss of Id1 increased osteoclast differentiation and resorption activity, both in vivo and in vitro, suggesting a cell autonomous role for Id1 as a negative regulator of osteoclast differentiation. Examination by flow cytometry of the hematopoietic compartment of Id1−/− mice showed an increase in myeloid differentiation. Additionally, we found increased expression of osteoclast genes, TRAP, Oscar, and CTSK in the Id1−/− bone marrow microenvironment. Lastly, transplantation of wild-type bone marrow into Id1−/− mice repressed TRAP, Oscar, and CTSK expression and activity and rescued the hematopoietic and bone phenotype in these mice. In conclusion, we demonstrate an osteoporotic phenotype in Id1−/− mice and a mechanism for Id1 transcriptional control of osteoclast-associated genes. Our results identify Id1 as a principal player responsible for the dynamic cross-talk between bone and bone marrow hematopoietic cells.
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影响因子：
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作者：
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