Dynamics and cellular localization of Bmp2, Bmp4, and Noggin transcription in the postnatal mouse skeleton.
Dynamics and cellular localization of Bmp2, Bmp4, and Noggin transcription in the postnatal mouse skeleton.
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DOI：
10.1002/jbmr.2313
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发表时间：
2015-01
期刊：
影响因子：
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通讯作者：
Mortlock DP
中科院分区：
文献类型：
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作者：
Pregizer SK;Mortlock DP
骨形态发生蛋白（BMPs）及其拮抗剂在精确时空模式中的转录对于骨骼的正常发育、成熟、维持和修复是必不可少的。然而，这些分子在胚胎发生后的骨骼组织中的转录活性尚未得到很好的表征。在这项研究中，我们使用了几个转基因报告小鼠系，以确定两个有效的BMP配体，BMP 2和BMP 4，和他们的拮抗剂头蛋白在出生后骨骼的转录活性。在3-4周龄时，Bmp 4和Noggin报告基因活性分别在成骨或成软骨谱系的大多数细胞中很明显，而Bmp 2报告基因活性在这两个谱系的终末分化细胞中最强。到5-6个月时，报告基因的活性普遍减弱;然而，Noggin和Bmp 2报告基因在关节软骨细胞中保持显著活性，并无限期地持续存在。我们进一步发现，出生后骨和软骨中的内源性Bmp 2、Bmp 4和Noggin转录水平反映了这些组织中各自报告基因的活性。最后，我们发现在骨和软骨中的Bmp 2、Bmp 4和头蛋白报告基因在3-4周的活性可以在成骨和软骨形成培养模型中重现。这些结果表明，Bmp 2，Bmp 4和Noggin转录持续到不同程度的骨骼组织出生后，每个基因表现出自己的细胞类型的特定模式的活动。阐明这些模式及其动力学将指导未来的研究，旨在阐明出生后骨骼中异常BMP信号传导的原因和后果。
Transcription of Bone Morphogenetic Proteins (BMPs) and their antagonists in precise spatiotemporal patterns is essential for proper skeletal development, maturation, maintenance, and repair. Nevertheless, transcriptional activity of these molecules in skeletal tissues beyond embryogenesis has not been well-characterized. In this study, we used several transgenic reporter mouse lines to define the transcriptional activity of two potent BMP ligands, Bmp2 and Bmp4, and their antagonist Noggin in the postnatal skeleton. At 3–4 weeks of age, Bmp4 and Noggin reporter activity was readily apparent in most cells of the osteogenic or chondrogenic lineages, respectively, while Bmp2 reporter activity was strongest in terminally differentiated cells of both lineages. By 5–6 months, activity of the reporters had generally abated; however, the Noggin and Bmp2 reporters remained remarkably active in articular chondrocytes and persisted there indefinitely. We further found that endogenous Bmp2, Bmp4, and Noggin transcript levels in postnatal bone and cartilage mirrored the activity of their respective reporters in these tissues. Finally, we found that the activity of the Bmp2, Bmp4, and Noggin reporters in bone and cartilage at 3–4 weeks could be recapitulated in both osteogenic and chondrogenic culture models. These results reveal that Bmp2, Bmp4, and Noggin transcription persists to varying degrees in skeletal tissues postnatally, with each gene exhibiting its own cell-type specific pattern of activity. Illuminating these patterns and their dynamics will guide future studies aimed at elucidating both the causes and consequences of aberrant BMP signaling in the postnatal skeleton.