Primary cilia support cartilage regeneration after injury.
Primary cilia support cartilage regeneration after injury.
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DOI：
10.1038/s41368-023-00223-6
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发表时间：
2023-06-02
影响因子：
14.9
通讯作者：
Sun, Yao
中科院分区：
文献类型：
--
作者：
Tao, Dike;Zhang, Lei;Ding, Yunpeng;Tang, Na;Xu, Xiaoqiao;Li, Gongchen;Niu, Pingping;Yue, Rui;Wang, Xiaogang;Shen, Yidong;Sun, Yao
在成长中的儿童中，生长板软骨在骨折损伤后具有有限的自我修复能力，总是导致肢体生长停滞。有趣的是，生长板内的一种骨折损伤实现了惊人的自我愈合，然而，其机制尚不清楚。利用这种骨折小鼠模型，我们发现Hedgehog（Hh）信号在损伤的生长板中被激活，它可以激活生长板中的软骨细胞，促进软骨修复。初级纤毛是Hh信号传导的中心转导介质。值得注意的是，纤毛Hh-Smo-Gli信号通路在发育期间在生长板中富集。此外，生长板修复过程中，静止区和增殖区的软骨细胞动态纤毛。此外，条件性删除纤毛核心基因Ift 140在软骨破坏纤毛介导的Hh信号在生长板。更重要的是，通过Smoothened激动剂（SAG）激活纤毛Hh信号传导显著加速损伤后生长板的修复。总之，初级纤毛介导的Hh信号诱导干/祖软骨细胞的活化和骨折损伤后生长板修复。
In growing children, growth plate cartilage has limited self-repair ability upon fracture injury always leading to limb growth arrest. Interestingly, one type of fracture injuries within the growth plate achieve amazing self-healing, however, the mechanism is unclear. Using this type of fracture mouse model, we discovered the activation of Hedgehog (Hh) signaling in the injured growth plate, which could activate chondrocytes in growth plate and promote cartilage repair. Primary cilia are the central transduction mediator of Hh signaling. Notably, ciliary Hh-Smo-Gli signaling pathways were enriched in the growth plate during development. Moreover, chondrocytes in resting and proliferating zone were dynamically ciliated during growth plate repair. Furthermore, conditional deletion of the ciliary core gene Ift140 in cartilage disrupted cilia-mediated Hh signaling in growth plate. More importantly, activating ciliary Hh signaling by Smoothened agonist (SAG) significantly accelerated growth plate repair after injury. In sum, primary cilia mediate Hh signaling induced the activation of stem/progenitor chondrocytes and growth plate repair after fracture injury.
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DOI：
10.1002/jor.24017
发表时间：
2019-01
期刊：
Journal of orthopaedic research : official publication of the Orthopaedic Research Society
影响因子：
--
作者：
McKenzie JA;Maschhoff C;Liu X;Migotsky N;Silva MJ;Gardner MJ
通讯作者：
Gardner MJ
洞悉骨骼干细胞。
影响因子：
12.7
作者：
Li, Qiwen;Xu, Ruoshi;Lei, Kexin;Yuan, Quan
通讯作者：
Yuan, Quan
影响因子：
64.5
作者：
Kopinke D;Roberson EC;Reiter JF
通讯作者：
Reiter JF
影响因子：
4.6
作者：
Hilton, MJ;Tu, XL;Long, FX
通讯作者：
Long, FX
影响因子：
7.7
作者：
Hallett SA;Matsushita Y;Ono W;Sakagami N;Mizuhashi K;Tokavanich N;Nagata M;Zhou A;Hirai T;Kronenberg HM;Ono N
通讯作者：
Ono N