IFT20 is required for the maintenance of cartilaginous matrix in condylar cartilage

Abstract

Condylar cartilage is a joint cartilage essential for smooth jaw movement. The importance of ciliary proteins in condylar cartilage development has been reported. However, little is known about how ciliary proteins control the homeostasis of condylar cartilage. Here we show that intraflagellar transport 20 (IFT20), a ciliary protein, is required for the maintenance of cartilaginous matrix in condylar cartilage. Utilizing NG2-CreER mice expressed in condylar cartilage, we deleted Ift20 by tamoxifen treatment at juvenile-to-adult stages. In wild-type condylar cartilage, IFT20 was robustly produced in the cis-Golgi, but deletion of Ift20 by tamoxifen induction of NG2-CreER (Ift20:NG2-CreER) resulted in reduced cell proliferation and decreased Golgi size in condylar cartilage. Importantly, while the primary cilia were present in cartilage cells in the condylar layers of wild-type mice, no primary cilia were present in the Ift20:NG2-CreER condylar layers. Consistent with this finding, ciliary-mediated Hedgehog signaling was severely attenuated in Ift20 mutant chondrocytes, and thus the production levels of type X collagen were significantly reduced in Ift20:NG2-CreER mice. These results suggest that IFT20 is required for Golgi size and Hedgehog signaling to maintain cartilaginous matrix in condylar cartilage. Our study highlights the unique function of IFT20 in the homeostasis of condylar cartilage.

Dissecting the Vesicular Trafficking Function of IFT Subunits

“…Because the mice with neural crest-specific deletion of IFT20 died shortly after birth due to difficulties in feeding and breathing, another mouse line with chondrocyte-specific deletion of IFT20 at juvenile-to-adult stages was obtained (Kitami et al, 2018). In accordance with the previous studies, the maturation process of condylar cartilage was disrupted, owing to the lower amount of collagen type X and reduced proliferation.…”

Regulation of the Extracellular Matrix by Ciliary Machinery

“…These observations possibly rule out GMAP210-related defects in the collagen secretion phenotype, despite this mutation also resulting in impaired glycosylation and secretion of non-collagenous matrix molecules, namely perlecan. Kitami et al found that IFT20 knockout in adult mouse cartilage leads to loss of cilia, Hh signalling defects, and, in contrast to developmental IFT20 deletion, Golgi morphological changes due to altered input and output of cargo [63]. These morphological changes and decreased secretion are also observed in GMAP210 mutant patient-derived cells, indicating that these defects may be related more to changes in global secretory load, than specific, IFT20-mediated, trafficking from the Golgi [64].…”

Primary cilia: Versatile regulator in cartilage development

“…G, The potential mechanism of IFT20 is to regulate the Golgi size and Hedgehog signalling transduction to control the maintenance of the condylar cartilage. Reprinted with permission from Ref . Copyright 2019 Elsevier…”