BMP receptor signaling is required for postnatal maintenance of articular cartilage.
BMP receptor signaling is required for postnatal maintenance of articular cartilage.
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DOI：
10.1371/journal.pbio.0020355
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发表时间：
2004-11
期刊：
影响因子：
9.8
通讯作者：
Kingsley DM
中科院分区：
文献类型：
--
作者：
Rountree RB;Schoor M;Chen H;Marks ME;Harley V;Mishina Y;Kingsley DM
关节软骨在健康和流动性中起着至关重要的作用，但在数百万患有关节炎的人中经常受损或丢失。创造和维持覆盖关节区域骨骼表面的软骨薄层的分子机制知之甚少，部分原因是还没有专门操纵该组织中基因表达的工具。在这里，我们使用来自小鼠Gdf 5基因（骨形态发生蛋白[BMP]家族成员）的调控信息来开发新的小鼠品系，这些小鼠品系可用于激活或抑制关节发育中的基因。来自Gdf 5细菌人工染色体克隆的Cre重组酶的表达导致发育中的关节中floxed靶基因的特异性激活或失活，包括早期关节间带、成人关节软骨和关节囊。我们已经使用这个系统来测试BMP受体信号在关节发育中的作用。已知Bmpr 1a无效突变的小鼠在胚胎发育早期死亡，并伴有多种缺陷。然而，将floxed Bmpr 1a等位基因与Gdf 5-Cre驱动程序相结合绕过了这种胚胎致死性，并导致在关节区域缺失Bmpr 1a基因的小鼠的出生和出生后发育。身体中的大多数关节在没有Bmpr 1a受体功能的情况下正常形成。然而，受体缺陷小鼠出生后关节内的关节软骨在类似于人类骨关节炎的过程中逐渐磨损。Gdf 5-Cre小鼠提供了一个通用系统，可用于测试基因在关节区域中的作用。BMP受体信号不仅是多种组织的早期发育和创造所必需的，而且也是出生后关节软骨持续维持所必需的。BMP受体信号强度的遗传变异可能是人类骨关节炎的一个重要风险因素，应研究模拟或增强BMP受体信号的治疗方法，作为维持关节衬里健康的可能治疗策略。通过基因操作，这些作者减少了关节区域骨形态发生因子的信号传导，并为关节炎的研究创造了一个有价值的模型
Articular cartilage plays an essential role in health and mobility, but is frequently damaged or lost in millions of people that develop arthritis. The molecular mechanisms that create and maintain this thin layer of cartilage that covers the surface of bones in joint regions are poorly understood, in part because tools to manipulate gene expression specifically in this tissue have not been available. Here we use regulatory information from the mouse Gdf5 gene (a bone morphogenetic protein [BMP] family member) to develop new mouse lines that can be used to either activate or inactivate genes specifically in developing joints. Expression of Cre recombinase from Gdf5 bacterial artificial chromosome clones leads to specific activation or inactivation of floxed target genes in developing joints, including early joint interzones, adult articular cartilage, and the joint capsule. We have used this system to test the role of BMP receptor signaling in joint development. Mice with null mutations in Bmpr1a are known to die early in embryogenesis with multiple defects. However, combining a floxed Bmpr1a allele with the Gdf5-Cre driver bypasses this embryonic lethality, and leads to birth and postnatal development of mice missing the Bmpr1a gene in articular regions. Most joints in the body form normally in the absence of Bmpr1a receptor function. However, articular cartilage within the joints gradually wears away in receptor-deficient mice after birth in a process resembling human osteoarthritis. Gdf5-Cre mice provide a general system that can be used to test the role of genes in articular regions. BMP receptor signaling is required not only for early development and creation of multiple tissues, but also for ongoing maintenance of articular cartilage after birth. Genetic variation in the strength of BMP receptor signaling may be an important risk factor in human osteoarthritis, and treatments that mimic or augment BMP receptor signaling should be investigated as a possible therapeutic strategy for maintaining the health of joint linings. Through genetic manipulation, these authors have reduced signaling by bone morphogenetic factors in joint regions, and created a valuable model for the study of arthritis
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DOI：
10.1083/jcb.140.2.409
发表时间：
1998-01-26
期刊：
The Journal of cell biology
影响因子：
--
作者：
Enomoto-Iwamoto M;Iwamoto M;Mukudai Y;Kawakami Y;Nohno T;Higuchi Y;Takemoto S;Ohuchi H;Noji S;Kurisu K
通讯作者：
Kurisu K
影响因子：
--
作者：
Fernández-Lloris, R;Viñals, F;Ventura, F
通讯作者：
Ventura, F
影响因子：
6.2
作者：
Bau, B;Haag, J;Aigner, T
通讯作者：
Aigner, T
DOI：
10.1186/ar380
发表时间：
2002
期刊：
Arthritis research
影响因子：
--
作者：
Eyre D
通讯作者：
Eyre D
影响因子：
2.7
作者：
Chimal-Monroy, J;Rodriguez-Leon, J;Hurle, JM
通讯作者：
Hurle, JM