Human with bi-allelic WNT10A mutations and epithelial Wnt10a knockout mice present enlarged pulp chamber and apical displacement of the root furcation of multi-rooted teeth,known as taurodontism;thus,indicating the cr...Human with bi-allelic WNT10A mutations and epithelial Wnt10a knockout mice present enlarged pulp chamber and apical displacement of the root furcation of multi-rooted teeth,known as taurodontism;thus,indicating the critical role of Wnt10a in tooth root morphogenesis.However,the endogenous mechanism by which epithelial Wnt10a regulates Hertwig’s epithelial root sheath(HERS)cellular behaviors and contributes to root furcation patterning remains unclear.In this study,we found that HERS in the presumptive root furcating region failed to elongate at an appropriate horizontal level in K14-Cre;Wnt10a^(fl/fl)mice from post-natal day 0.5(PN0.5)to PN4.5.EdU assays and immunofluorescent staining of cyclin D1 revealed significantly decreased proliferation activity of inner enamel epithelial(IEE)cells of HERS in K14-Cre;Wnt10a^(fl/fl)mice at PN2.5 and PN3.5.Immunofluorescent staining of E-Cadherin and acetyl-α-Tubulin demonstrated that the IEE cells of HERS tended to divide perpendicularly to the horizontal plane,which impaired the horizontal extension of HERS in the presumptive root furcating region of K14-Cre;Wnt10a^(fl/fl)mice.RNA-seq and immunofluorescence showed that the expressions of Jag1 and Notch2 were downregulated in IEE cells of HERS in K14-Cre;Wnt10a^(fl/fl)mice.Furthermore,after activation of Notch signaling in K14-Cre;Wnt10a^(fl/fl)molars by Notch2 adenovirus and kidney capsule grafts,the root furcation defect was partially rescued.Taken together,our study demonstrates that an epithelial Wnt10a-Notch signaling axis is crucial for modulating HERS cell proper proliferation and horizontal-oriented division during tooth root furcation morphogenesis.展开更多
目的:探讨无翅型MMTV整合位点家族成员10a(Wnt10a)在甲状腺乳头状癌(papillary thyroid carcinoma,PTC)和桥本合并甲状腺乳头癌(Hashimoto's thyroiditis associated with papillary thyroid carcinoma)中的表达及其临床意义。方法...目的:探讨无翅型MMTV整合位点家族成员10a(Wnt10a)在甲状腺乳头状癌(papillary thyroid carcinoma,PTC)和桥本合并甲状腺乳头癌(Hashimoto's thyroiditis associated with papillary thyroid carcinoma)中的表达及其临床意义。方法:采用q RT-PCR方法检测Wnt10a m RNA在41例新鲜甲状腺组织(PTC组织18例,HT合并PTC组织12例,结节性甲状腺肿组织11例)中的表达;用免疫组化SP法检测Wnt10a蛋白在50例甲状腺石蜡标本(PTC组织20例,HT合并PTC组织20例,结节性甲状腺肿组织10例)中的表达。结果:1 RT-PCR Wnt10a m RNA在甲状腺癌组织中的表达明显高于其在良性甲状腺肿瘤组织中的表达(P<0.01),差异有显著性;Wnt10a m RNA在PTC、HT合并PTC组织中的阳性表达强度分别为2.49×10-5(0.68×10-5,15.28×10-5),1.26×10-5(0.97×10-5,13.73×10-5);P<0.05,差异具有显著性。Wnt10a m RNA在PTC、HT合并PTC组织中的表达分别是结节性甲状腺肿组织的9.98、2.69倍。2SP法:Wnt10a在甲状腺癌组织中的表达明显高于其在良性甲状腺肿瘤组织中的表达。Wnt10a m RNA和蛋白在甲状腺癌组织中的表达与肿瘤大小、临床分期、淋巴结转移等临床因素无明显关系(P>0.05),只与甲状腺癌组织的病理分型相关,(P<0.05)。结论:Wnt10a在甲状腺乳头状癌和桥本合并甲状腺乳头癌中呈现高表达,且有差异性,有望作为甲状腺癌的病理分型的参考指标,有助于甲状腺癌的早期诊断及病理分型的判定,使患者得到及时有效治疗。展开更多
基金supported by the National Natural Science Foundation of China(82270944,82100976,82071076 and 81600846).
文摘Human with bi-allelic WNT10A mutations and epithelial Wnt10a knockout mice present enlarged pulp chamber and apical displacement of the root furcation of multi-rooted teeth,known as taurodontism;thus,indicating the critical role of Wnt10a in tooth root morphogenesis.However,the endogenous mechanism by which epithelial Wnt10a regulates Hertwig’s epithelial root sheath(HERS)cellular behaviors and contributes to root furcation patterning remains unclear.In this study,we found that HERS in the presumptive root furcating region failed to elongate at an appropriate horizontal level in K14-Cre;Wnt10a^(fl/fl)mice from post-natal day 0.5(PN0.5)to PN4.5.EdU assays and immunofluorescent staining of cyclin D1 revealed significantly decreased proliferation activity of inner enamel epithelial(IEE)cells of HERS in K14-Cre;Wnt10a^(fl/fl)mice at PN2.5 and PN3.5.Immunofluorescent staining of E-Cadherin and acetyl-α-Tubulin demonstrated that the IEE cells of HERS tended to divide perpendicularly to the horizontal plane,which impaired the horizontal extension of HERS in the presumptive root furcating region of K14-Cre;Wnt10a^(fl/fl)mice.RNA-seq and immunofluorescence showed that the expressions of Jag1 and Notch2 were downregulated in IEE cells of HERS in K14-Cre;Wnt10a^(fl/fl)mice.Furthermore,after activation of Notch signaling in K14-Cre;Wnt10a^(fl/fl)molars by Notch2 adenovirus and kidney capsule grafts,the root furcation defect was partially rescued.Taken together,our study demonstrates that an epithelial Wnt10a-Notch signaling axis is crucial for modulating HERS cell proper proliferation and horizontal-oriented division during tooth root furcation morphogenesis.
文摘目的:探讨无翅型MMTV整合位点家族成员10a(Wnt10a)在甲状腺乳头状癌(papillary thyroid carcinoma,PTC)和桥本合并甲状腺乳头癌(Hashimoto's thyroiditis associated with papillary thyroid carcinoma)中的表达及其临床意义。方法:采用q RT-PCR方法检测Wnt10a m RNA在41例新鲜甲状腺组织(PTC组织18例,HT合并PTC组织12例,结节性甲状腺肿组织11例)中的表达;用免疫组化SP法检测Wnt10a蛋白在50例甲状腺石蜡标本(PTC组织20例,HT合并PTC组织20例,结节性甲状腺肿组织10例)中的表达。结果:1 RT-PCR Wnt10a m RNA在甲状腺癌组织中的表达明显高于其在良性甲状腺肿瘤组织中的表达(P<0.01),差异有显著性;Wnt10a m RNA在PTC、HT合并PTC组织中的阳性表达强度分别为2.49×10-5(0.68×10-5,15.28×10-5),1.26×10-5(0.97×10-5,13.73×10-5);P<0.05,差异具有显著性。Wnt10a m RNA在PTC、HT合并PTC组织中的表达分别是结节性甲状腺肿组织的9.98、2.69倍。2SP法:Wnt10a在甲状腺癌组织中的表达明显高于其在良性甲状腺肿瘤组织中的表达。Wnt10a m RNA和蛋白在甲状腺癌组织中的表达与肿瘤大小、临床分期、淋巴结转移等临床因素无明显关系(P>0.05),只与甲状腺癌组织的病理分型相关,(P<0.05)。结论:Wnt10a在甲状腺乳头状癌和桥本合并甲状腺乳头癌中呈现高表达,且有差异性,有望作为甲状腺癌的病理分型的参考指标,有助于甲状腺癌的早期诊断及病理分型的判定,使患者得到及时有效治疗。
