IFT20 is critical for collagen biosynthesis in craniofacial bone formation.
IFT20 is critical for collagen biosynthesis in craniofacial bone formation.
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IFT20对于颅面骨形成中的胶原蛋白生物合成至关重要。
DOI：
10.1016/j.bbrc.2020.09.033
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发表时间：
2020-12-17
影响因子：
3.1
通讯作者：
Komatsu Y
中科院分区：
文献类型：
--
作者：
Yamaguchi H;Terajima M;Kitami M;Wang J;He L;Saeki M;Yamauchi M;Komatsu Y
鞭毛内运输（IFT）对于骨形成所需的初级纤毛的组装是必不可少的。IFT的破坏经常导致人类的骨缺损。虽然IFT在成骨细胞增殖和分化中的作用已经得到了很好的研究，但它在骨形成过程中胶原生物合成中的作用却知之甚少。本研究表明，IFT20是IFT- b复合物中最小的IFT蛋白，对小鼠胶原蛋白的生物合成很重要。颅面成骨细胞中Ift20的缺失表现为面部骨缺损。虽然胶原蛋白水平不受Ift20缺失的影响，但胶原交联明显改变。在Ift20:Wnt1-Cre和Ift20:Ocn-Cre小鼠中，骨骼表现出羟基赖氨酸-醛衍生交联增加，赖氨酸-醛衍生交联减少。为了深入了解分子机制，我们检测了末端肽基赖基羟化酶2 （LH2）和相关伴侣复合物的表达水平。结果表明，虽然LH2水平不受Ift20缺失的影响，但其伴侣FKBP65在Ift20:Wnt1-Cre和Ift20:Ocn-Cre小鼠颅骨和股骨中显著升高。这些结果表明，IFT20通过部分调节骨中末端肽基赖氨酸羟基化和交联在胶原生物合成中起关键作用。据我们所知，这是第一次证明IFT成分控制胶原翻译后修饰。这为与颅面骨性纤毛病相关的颅面骨缺损提供了新的见解。
Intraflagellar transport (IFT) is essential for assembling primary cilia required for bone formation. Disruption of IFT frequently leads to bone defects in humans. While it has been well studied about the function of IFT in osteogenic cell proliferation and differentiation, little is known about its role in collagen biosynthesis during bone formation. Here we show that IFT20, the smallest IFT protein in the IFT-B complex, is important for collagen biosynthesis in mice. Deletion of Ift20 in craniofacial osteoblasts displayed bone defects in the face. While collagen protein levels are unaffected by loss of Ift20, collagen cross-linking was significantly altered. In both Ift20:Wnt1-Cre and Ift20:Ocn-Cre mice the bones exhibit increased hydroxylysine-aldehyde deived cross-linking, and decreased lysine-aldehyde derived cross-linking. To obtain insight into the molecular mechanisms, we examined the expression levels of telopeptidyl lysyl hydroxylase 2 (LH2), and associated chaperone complexes. The results demonstrated that, while LH2 levels were unaffected by loss of Ift20, its chaperone, FKBP65, was significantly increased in Ift20:Wnt1-Cre and Ift20:Ocn-Cre mouse calvaria as well as femurs. These results suggest that IFT20 plays a pivotal role in collagen biosynthesis by regulating, in part, telopeptidyl lysine hydroxylation and cross-linking in bone. To the best of our knowledge, this is the first to demonstrate that the IFT components control collagen post-translational modifications. This provides a novel insight into the craniofacial bone defects associated with craniofacial skeletal ciliopathies.
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影响因子：
4.5
作者：
Heard ME;Besio R;Weis M;Rai J;Hudson DM;Dimori M;Zimmerman SM;Kamykowski JA;Hogue WR;Swain FL;Burdine MS;Mackintosh SG;Tackett AJ;Suva LJ;Eyre DR;Morello R
通讯作者：
Morello R
影响因子：
4.5
作者：
Cabral WA;Perdivara I;Weis M;Terajima M;Blissett AR;Chang W;Perosky JE;Makareeva EN;Mertz EL;Leikin S;Tomer KB;Kozloff KM;Eyre DR;Yamauchi M;Marini JC
通讯作者：
Marini JC
DOI：
10.1073/pnas.1600074113
发表时间：
2016-06-28
影响因子：
11.1
作者：
Gjaltema, Rutger A. F.;van der Stoel, Miesje M.;Bank, Ruud A.
通讯作者：
Bank, Ruud A.
通过控制软骨细胞分化和功能中TGF-β信号传导的调节，需要骨折愈合需要IFT80。
DOI：
10.1002/jbmr.3902
发表时间：
2020-03
期刊：
Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research
影响因子：
--
作者：
Liu M;Alharbi M;Graves D;Yang S
通讯作者：
Yang S
DOI：
10.1073/pnas.96.3.1054
发表时间：
1999-02-02
影响因子：
11.1
作者：
Bank, RA;Robins, SP;TeKoppele, JM
通讯作者：
TeKoppele, JM