Li Lili, Liu Peihong, Lv Xuechao, Yu Tianliang, Jin Xingai, Wang Rui, Xie Xiaohua, Wang Qingshan, Liu Yingqun, Saiyin Wuliji
Department of Stomatology, The First Affiliated Hospital of Harbin Medical University, 23 Youzheng Road, Nangang, 150086, Harbin, Heilongjiang, China.
Institute of Hard Tissue Development and Regeneration, The Second Affiliated Hospital of Harbin Medical University, 150001, Harbin, Heilongjiang, China.
J Orofac Orthop. 2023 Nov;84(6):349-361. doi: 10.1007/s00056-022-00386-7. Epub 2022 Mar 22.
Short root defects are prone to cause various periodontal diseases and lead to tooth loss in some serious cases. Studies about the mechanisms governing the development of the root are needed for a better understanding of the pathogenesis of short root defects. The protein family with sequence similarity 20 group C (FAM20C) is a Golgi casein kinase that has been well studied in the development of tooth crown formation. However, whether FAM20C plays a role in the development of tooth root is still unknown. Thus, we generated Sox2-Cre;Fam20c (cKO) mice, in which Fam20c was ablated in both the dental epithelium and dental mesenchyme, and found that the cKO mice showed severe short root defects mainly by inhibiting the development of dental mesenchyme in the root region. In this investigation, we found morphological changes and differentiation defects, with reduced expression of dentin sialophosphoprotein (DSPP) in odontoblasts of the root region in cKO mice. Furthermore, the proliferation rate of apical papillary cells was reduced in the root of cKO mice. In addition, the levels of bone morphogenetic protein 4 (BMP4) and phospho-Smad1/5/8, and that of Osterix and Krüppel-like factor 4 (KLF4), two downstream target molecules of the BMP signaling pathway, were significantly reduced in the root of cKO mice. These results indicate that FAM20C plays an essential role in the development of the root by regulating the BMP signaling pathway.
短根缺陷容易引发各种牙周疾病，在某些严重情况下会导致牙齿脱落。为了更好地理解短根缺陷的发病机制，需要对调控牙根发育的机制进行研究。序列相似性20家族C组（FAM20C）蛋白是一种高尔基体酪蛋白激酶，在牙冠形成发育方面已有充分研究。然而，FAM20C在牙根发育中是否发挥作用仍不清楚。因此，我们构建了Sox2-Cre;Fam20c（cKO）小鼠，其中Fam20c在牙上皮和牙间充质中均被敲除，结果发现cKO小鼠表现出严重的短根缺陷，主要是通过抑制牙根区域牙间充质的发育。在本研究中，我们发现cKO小鼠牙根区域成牙本质细胞中牙本质涎磷蛋白（DSPP）表达降低，出现形态学改变和分化缺陷。此外，cKO小鼠牙根中根尖乳头细胞的增殖率降低。另外，cKO小鼠牙根中骨形态发生蛋白4（BMP4）和磷酸化Smad1/5/8以及BMP信号通路的两个下游靶分子Osterix和Krüppel样因子4（KLF4）的水平均显著降低。这些结果表明，FAM20C通过调控BMP信号通路在牙根发育中发挥重要作用。
