講演情報
[P25-1]Oclulo-facio-cardio-dental症候群における歯根形態異常発症に関する分子メカニズムについて
○小川 卓也, KYAW MIN SOE, 森山 啓司 (東京医科歯科大学 大学院医歯学総合研究科 顎顔面矯正学分野)
Mutations in the B-cell lymphoma 6 (BCL6) interacting corepressor (BCOR) cause oculo-facio-cardio-dental (OFCD) syndrome, a rare X-linked dominant condition that includes dental radiculomegaly among other characteristics. BCOR regulates downstream genes via BCL6 as a transcriptional corepressor. This study aimed to identify BCOR-regulated genetic pathways in radiculomegaly. The microarray profile of affected tissues revealed that the gene-specific transcriptional factors group, wherein nucleus factor 1B, distal-less homeobox 5, and zinc finger protein multitype 2 (ZFPM2) were the most upregulated, was significantly expressed in periodontal ligament (PDL) cells of the diseased patient with a frameshift mutation (c.3668delC) in BCOR. Wild-type BCOR overexpression in human periodontal ligament fibroblasts cells significantly hampered cellular proliferation and ZFPM2 mRNA downregulation. Promotor binding assays showed that wild-type BCOR was recruited in the BCL6 binding of the ZFPM2 promotor region after immunoprecipitation, while mutant BCOR, which was the same genotype as our patient, failed to recruit these promotor regions. Knockdown of ZFPM2 expression in mutant PDL cells significantly reduced cellular proliferation as well as mRNA expression of alkaline phosphatase, an important marker of odontoblasts and cementoblasts. Collectively, our findings suggest that BCOR mutation-induced ZFPM2 regulation via BCL6 possibly contributes to hyperactive root formation in OFCD syndrome.