条件性敲除Fam20C对小鼠牙周膜内MMP-1及TIMP-1表达的影响  

Effect of Conditional Knockout of Fam20C on Expression of MMP-1 and TIMP-1 in Periodontal Ligament of Mice

作　　者：袁朝阳 吴国栋 祁皓 马肃[1,3] 刘培红[1,3] YUAN Zhaoyang;WU Guodong;QI Hao;MA Su;LIU Peihong(Department of Periodontics, The First Affiliated Hospital of Harbin Medical University, School of Stomatology, Harbin Medical University, Harbin 150001, China;The Key Laboratory of Cardiovascular Disease Acousto-Optic Electromagnetic Diagnosis and Treatment in Heilongjiang Province, Harbin 150001, China;Longjiang Scholars Laboratory, The First Affiliated Hospital of Harbin Medical University, Harbin 150001, China)

机构地区：[1]哈尔滨医科大学附属第一医院哈尔滨医科大学口腔医学院牙周科,黑龙江哈尔滨150001 [2]黑龙江省心血管病声光电磁诊疗重点实验室,黑龙江哈尔滨150001 [3]哈尔滨医科大学附属第一医院龙江学者实验室,黑龙江哈尔滨150001

出　　处：《口腔医学研究》2022年第5期417-423,共7页Journal of Oral Science Research

基　　金：黑龙江省自然科学基金面上项目(编号:H2017030);哈尔滨医科大学附属第一医院科研基金(编号:2016B020)。

摘　　要：目的:探讨3.6 kb Col1α1启动子驱动下敲除Fam20C对小鼠牙周组织的影响。方法:取4周龄和12周龄3.6 kb Col1α1-Cre;Fam20C^(fl/fl)小鼠和同窝正常对照小鼠下颌骨组织蜡块,常规制作下颌磨牙区石蜡切片,分别进行HE染色、Masson染色和免疫组织化学染色。观察两组小鼠磨牙区牙骨质、牙槽骨和牙周膜的组织学变化,测量光密度值分析牙周膜内MMP-1和TIMP-1的差异表达,SPSS 26.0统计软件对各组数据行独立样本t检验。结果:与正常对照小鼠相比,4周龄Fam20C敲除小鼠磨牙区细胞牙骨质变薄;磨牙间牙槽骨高度降低;牙周膜胶原纤维束直径减小,部分纤维束排列疏松无序;牙周膜内MMP-1阳性表达显著增加(P<0.05),TIMP-1阳性表达少量降低(P>0.05),MMP-1/TIMP-1比值显著增加(P<0.05)。12周龄Fam20C敲除小鼠较4周龄敲除小鼠牙周组织病变严重,细胞牙骨质显著减少;磨牙间牙槽骨高度明显降低;牙周膜胶原纤维束更加纤细稀疏、排列紊乱,根颈部下方大量胶原纤维束断裂,与牙骨质和牙槽骨表面脱离;牙周膜内MMP-1和TIMP-1的差异表达趋势与4周龄组一致。结论:3.6 kb Col1α1启动子驱动下敲除Fam20C可能通过上调牙周膜内MMP-1/TIMP-1比值导致小鼠牙周病变。Objective:To investigate the effect of knocking down Fam20C driven by the 3.6 kb Col1α1 promoter on periodontal tissues in mice.Methods:Paraffin sections of the mandibular molar region were routinely made from paraffin blocks of mandibular tissues of 3.6 kb Col1α1-Cre;Fam20C^(fl/fl) mice and normal control mice in the same litter at 4 and 12 weeks of age.The paraffin sections were used for HE staining,Masson staining,and immunohistochemical staining.The histological changes of cementum,alveolar bone,and periodontal ligament in the molar region of mice in all groups were observed.Optical density values were measured to analyze the differential expression of MMP-1 and TIMP-1 in the periodontal ligament.Results:Compared with normal control mice,the cellular cementum in the molar area of 4-week-old Fam20C knockout mice became thinner;The height of alveolar bone between molars was reduced.The diameter of collagen fiber bundles in the periodontal ligament was decreased,and some fiber bundles were loose and disordered.The positive expression of MMP-1 in periodontal ligament was significantly increased(P<0.05).The positive expression of TIMP-1 was slightly decreased(P>0.05).The MMP-1/TIMP-1 ratio was significantly increased(P<0.05).12-week-old Fam20C knockout mice had more severe periodontal tissue lesions than 4-week-old knockout mice.Their cellular cementum was significantly decreased.The height of alveolar bone between molars was significantly reduced.The collagen fiber bundles of the periodontal ligament were disorganized.They were slenderer and sparse.A large number of collagen fiber bundles below the root neck were broken and detached from the surface of cementum and alveolar bone.The trend of differential expression of MMP-1 and TIMP-1 in the periodontal ligament was consistent with the 4-week-old group.Conclusion:The knockout of Fam20C driven by the 3.6 kb Col1α1 promoter may lead to periodontal lesions in mice by up-regulating the MMP-1/TIMP-1 ratio in the periodontal ligament.

关 键 词：Fam20C 条件性基因敲除 牙周膜 MMP-1 TIMP-1 

分 类 号：R78[医药卫生—口腔医学]