Primary cilia support cartilage regeneration after injury

Abstract

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.

Interaction between immuno-stem dual lineages in jaw bone formation and injury repair

“…The classical Hh signaling pathway relies on primary cilia for transduction, which is indispensable for bone development and repair. Moreover, primary ciliary signals are observed in immune cells ( TAO et al, 2023 ) ( Figure 4 ).…”

Recent advances in primary cilia in bone metabolism

“…In addition, due to the unique composition of cartilage, its restoration following an injury proves highly challenging. Recently,Tao ( 81 ) found that activation of ciliated Hh signaling by Smoothened agonists (SAG) when the growth plate is damaged significantly accelerates growth plate repair after injury, and his further study found that chondrocytes in the resting and proliferating zones are dynamically ciliated during growth plate repair. Furthermore, conditional deletion of the cilia core gene Ift140 in cartilage disrupts cilia-mediated Hh signaling in the growth plate.…”

The Role of Cilia in the Development, Survival, and Regeneration of Hair Cells

“…This is true of neurons in multiple brain regions including the cerebellum, hippocampus, and cortex (Amador-Arjona et al, 2011; Breunig et al, 2008; Chizhikov et al, 2007; Han et al, 2008; Pruski et al, 2019; Spassky et al, 2008; Tong et al, 2014). Decreases in cell proliferation are seen in cilia mutants in other cell types as well including Müller glia cells, oligodendrocyte precursors, chondrocytes, outer annulus fibroblasts cells, osteoblasts, embryonic fibroblasts, and dental pulp stem cells (Cullen et al, 2021; Ferraro et al, 2015; Kitami et al, 2019; Li, Yang, et al, 2020; Noda et al, 2016; Pruski et al, 2019; Song et al, 2007; Tao et al, 2023; Yuan et al, 2019).…”