Irizarry Armando R, Yan Guirui, Zeng Qingqiang, Lucchesi Jonathan, Hamang Matthew J, Ma Yanfei L, Rong James Xiaojun
Department of Pathology, Lilly Research Laboratories, Eli Lilly & Company, Indianapolis, IN, United States of America.
Lilly China R&D Center, Eli Lilly & Company, Building 8, No. 338, Zhangjiang Hi-Tech Park, Shanghai, People's Republic of China.
PLoS One. 2017 Apr 13;12(4):e0175465. doi: 10.1371/journal.pone.0175465. eCollection 2017.
There has been growing recognition of the essential roles of citrate in biomechanical properties of mineralized tissues, including teeth and bone. However, the sources of citrate in these tissues have not been well defined, and the contribution of citrate to the regulation of odontogenesis and osteogenesis has not been examined. Here, tooth and bone phenotypes were examined in sodium-dependent citrate transporter (NaCT) Slc13a5 deficient C57BL/6 mice at 13 and 32 weeks of age. Slc13a5 deficiency led to defective tooth development, characterized by absence of mature enamel, formation of aberrant enamel matrix, and dysplasia and hyperplasia of the enamel organ epithelium that progressed with age. These abnormalities were associated with fragile teeth with a possible predisposition to tooth abscesses. The lack of mature enamel was consistent with amelogenesis imperfecta. Furthermore, Slc13a5 deficiency led to decreased bone mineral density and impaired bone formation in 13-week-old mice but not in older mice. The findings revealed the potentially important role of citrate and Slc13a5 in the development and function of teeth and bone.
人们越来越认识到柠檬酸盐在矿化组织(包括牙齿和骨骼)的生物力学特性中起着至关重要的作用。然而,这些组织中柠檬酸盐的来源尚未明确界定,并且柠檬酸盐对牙发生和骨发生调节的贡献也未得到研究。在此,对13周龄和32周龄的钠依赖性柠檬酸盐转运体(NaCT)Slc13a5缺陷型C57BL/6小鼠的牙齿和骨骼表型进行了检查。Slc13a5缺陷导致牙齿发育缺陷,其特征为缺乏成熟釉质、形成异常釉基质以及随着年龄增长釉器上皮发育异常和增生。这些异常与脆弱的牙齿有关,可能易患牙脓肿。缺乏成熟釉质与釉质发育不全一致。此外,Slc13a5缺陷导致13周龄小鼠的骨矿物质密度降低和骨形成受损,但在老年小鼠中未出现这种情况。这些发现揭示了柠檬酸盐和Slc13a5在牙齿和骨骼发育及功能中的潜在重要作用。