Department of Pediatrics, The University of Texas Medical School at Houston, Houston, TX, 77030, USA.
Department of Pediatrics, The University of Texas Medical School at Houston, Houston, TX, 77030, USA; Division of Bioprosthodontics, Niigata University Graduate School of Medical and Dental Sciences, Niigata, 951-8514, Japan.
Biochem Biophys Res Commun. 2019 Jan 29;509(1):222-226. doi: 10.1016/j.bbrc.2018.12.107. Epub 2018 Dec 23.
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.
髁突软骨是一种关节软骨，对于下颌运动的顺畅至关重要。已经有报道称纤毛蛋白在髁突软骨发育中的重要性。然而，人们对于纤毛蛋白如何控制髁突软骨的动态平衡知之甚少。在这里，我们发现，鞭毛内运输 20（IFT20）是一种纤毛蛋白，对于髁突软骨中软骨基质的维持是必需的。利用在髁突软骨中表达的 NG2-CreER 小鼠，我们通过在幼年期至成年期用他莫昔芬处理来删除 Ift20。在野生型髁突软骨中，IFT20 在顺面高尔基体内大量产生，但用他莫昔芬诱导 NG2-CreER 来删除 Ift20（Ift20:NG2-CreER）导致髁突软骨中的细胞增殖减少和高尔基体积减小。重要的是，虽然在野生型小鼠的髁突层软骨细胞中有初级纤毛，但在 Ift20:NG2-CreER 髁突层中没有初级纤毛。与这一发现一致的是，纤毛介导的 Hedgehog 信号在 Ift20 突变的软骨细胞中严重减弱，因此 Ift20:NG2-CreER 小鼠中 X 型胶原的产生水平显著降低。这些结果表明，IFT20 对于高尔基体的大小和 Hedgehog 信号的传导对于维持髁突软骨中的软骨基质是必需的。我们的研究强调了 IFT20 在髁突软骨动态平衡中的独特功能。
