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Id1 抑制破骨细胞依赖性转录，并影响骨形成和造血。

Id1 represses osteoclast-dependent transcription and affects bone formation and hematopoiesis.

机构信息

Department of Pediatrics, Weill Cornell Medical College, New York, New York, United States of America.

出版信息

PLoS One. 2009 Nov 24;4(11):e7955. doi: 10.1371/journal.pone.0007955.

DOI:10.1371/journal.pone.0007955
PMID:19956687
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2776978/
Abstract

BACKGROUND

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.

METHODOLOGY/PRINCIPAL FINDINGS: 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.

CONCLUSIONS/SIGNIFICANCE: 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.

摘要

背景

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）和造血细胞在解剖上相邻。这些细胞的紧密接近自然表明它们相互作用，但这些相互作用才刚刚开始被描述。

方法/主要发现：使用 Id1(-/-) 小鼠模型来评估 Id1 在骨髓微环境中的作用。微计算机断层扫描和骨折测试表明，Id1(-/-) 小鼠的骨量减少，脆性增加，表现出骨质疏松症的表型。破骨细胞生成和陷窝形成测定显示，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剂具有细胞自主作用。通过流式细胞术对 Id1(-/-) 小鼠的造血部分进行检查显示，髓样分化增加。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，抑制了这些小鼠中 TRAP、Oscar 和 CTSK 的表达和活性，并挽救了这些小鼠的造血和骨骼表型。

结论

总之，我们在 Id1(-/-) 小鼠中证明了骨质疏松症的表型，并确定了 Id1 对破骨细胞相关基因的转录控制机制。我们的结果表明，Id1 是负责骨骼和骨髓造血细胞之间动态串扰的主要参与者。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1e5b/2776978/27feadac4638/pone.0007955.g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1e5b/2776978/e5c2a84b948a/pone.0007955.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1e5b/2776978/e34123bde998/pone.0007955.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1e5b/2776978/b29ea23a35dc/pone.0007955.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1e5b/2776978/888fc94e34e6/pone.0007955.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1e5b/2776978/4c11038840a7/pone.0007955.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1e5b/2776978/27feadac4638/pone.0007955.g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1e5b/2776978/e5c2a84b948a/pone.0007955.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1e5b/2776978/e34123bde998/pone.0007955.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1e5b/2776978/b29ea23a35dc/pone.0007955.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1e5b/2776978/888fc94e34e6/pone.0007955.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1e5b/2776978/4c11038840a7/pone.0007955.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1e5b/2776978/27feadac4638/pone.0007955.g006.jpg

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