Targeted Deletion of the Claudin12 Gene in Mice Increases Articular Cartilage and Inhibits Chondrocyte Differentiation.
Targeted Deletion of the Claudin12 Gene in Mice Increases Articular Cartilage and Inhibits Chondrocyte Differentiation.
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DOI：
10.3389/fendo.2022.931318
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发表时间：
2022
影响因子：
5.2
通讯作者：
Mohan, Subburaman
中科院分区：
文献类型：
--
作者：
Xing, Weirong;Pourteymoor, Sheila;Chen, Yian;Mohan, Subburaman
为了研究 Claudin (CLDN)12 在骨骼中的作用，我们培育了 Cldn12 基因中外显子 2 定向缺失的小鼠，用于骨骼表型分析。对 Cldn12 基因有针对性破坏的小鼠和对照同窝小鼠的股骨远端次生海绵体的微 CT 分析显示，13 周龄小鼠中任一性别的皮质骨或小梁骨参数均没有显着的基因型特异性差异。免疫组织化学显示，3周龄野生型小鼠的次级海绵组织的分化软骨细胞和成骨细胞中均表达CLDN12，但成年小鼠的表达仅限于关节软骨和生长板的分化软骨细胞。与对照同窝小鼠相比，Cldn12 敲除 (KO) 小鼠的膝关节软骨面积增加了 47%。 Micro-CT分析发现，虽然Cldn12 KO小鼠股骨骨骺的小梁数量增加了9%，小梁间距减少了9%，但两种基因型之间的骨量和根据组织体积调整的骨量均没有差异。与对照小鼠相比，来自 KO 的原代关节软骨细胞中 Clusterin、Lubricin 和 Mmp13 的表达水平分别增加了 56%、46% 和 129%。我们的数据表明，小鼠 Cldn12 基因的靶向缺失可部分通过促进关节软骨细胞表型来增加关节软骨。
To study the role of Claudin (CLDN)12 in bone, we developed mice with a targeted deletion of exon2 in the Cldn12 gene for skeletal phenotype analysis. Micro-CT analysis of the secondary spongiosa of distal femurs of mice with targeted disruption of the Cldn12 gene and control littermates showed no significant genotype-specific differences in either cortical or trabecular bone parameters for either gender in 13-week-old mice. Immunohistochemistry revealed that while CLDN12 was expressed in both differentiating chondrocytes and osteoblasts of the secondary spongiosa of 3-week-old wild-type mice, its expression was restricted to differentiating chondrocytes in the articular cartilage and growth plate in adult mice. Articular cartilage area at the knee were increased by 47% in Cldn12 knockout (KO) mice compared to control littermates. Micro-CT analyses found that while the trabecular number was increased by 9% and the trabecular spacing was reduced by 9% in the femoral epiphysis of Cldn12 KO mice, neither bone volume nor bone volume adjusted for tissue volume was different between the two genotypes. The expression levels of Clusterin, Lubricin and Mmp13 were increased by 56%, 46%, and 129%, respectively, in primary articular chondrocytes derived from KO compared to control mice. Our data indicate that targeted deletion of the Cldn12 gene in mice increases articular cartilage, in part, by promoting articular chondrocyte phenotype.
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三个紧密连接相关的Maguks ZO-1，ZO-2和ZO-3与Claudins的Cooh Termini直接结合。
DOI：
10.1083/jcb.147.6.1351
发表时间：
1999-12-13
期刊：
The Journal of cell biology
影响因子：
--
作者：
Itoh M;Furuse M;Morita K;Kubota K;Saitou M;Tsukita S
通讯作者：
Tsukita S
影响因子：
4.8
作者：
Nilsson, Ola;Weise, Martina;Baron, Jeffrey
通讯作者：
Baron, Jeffrey
影响因子：
7.8
作者：
Nitta, T;Hata, M;Tsukita, S
通讯作者：
Tsukita, S
影响因子：
4.1
作者：
Beamer, WG;Donahue, LR;Baylink, DJ
通讯作者：
Baylink, DJ
影响因子：
2.8
作者：
Stewart, Melanie K.;Mattiske, Deidre M.;Pask, Andrew J.
通讯作者：
Pask, Andrew J.