Department of Implantology, School & Hospital of Stomatology, Tongji University, Shanghai, China.
Shanghai Engineering Research Center of Tooth Restoration and Regeneration, Shanghai, China.
Int J Oral Sci. 2023 Jun 2;15(1):22. doi: 10.1038/s41368-023-00223-6.
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.
在生长中的儿童中，生长板软骨在骨折损伤后自我修复能力有限，这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能实现惊人的自我愈合，但机制尚不清楚。利用这种类型的骨折小鼠模型，我们发现，损伤的生长板中 Hedgehog（Hh）信号被激活，这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 信号的中央转导介质。值得注意的是，Hh-Smo-Gli 信号通路在发育过程中在生长板中富集。此外，在生长板修复过程中，静止区和增殖区的软骨细胞动态纤毛化。此外，软骨中纤毛核心基因 Ift140 的条件性缺失破坏了生长板中纤毛介导的 Hh 信号。更重要的是，通过 Smoothened 激动剂（SAG）激活纤毛 Hh 信号显著加速了损伤后的生长板修复。总之，初级纤毛介导 Hh 信号诱导了骨折损伤后干细胞/祖细胞软骨的激活和生长板修复。
