Lee Ji-Hyun, Lee Dong-Seol, Nam Hyun, Lee Gene, Seo Byoung-Moo, Cho Young-Sik, Bae Hyun-Sook, Park Joo-Cheol
Department of Oral Histology-Developmental Biology & Dental Research Institute, BK21 Project, School of Dentistry, Seoul National University, Seoul, South Korea.
Eur J Oral Sci. 2012 Feb;120(1):29-37. doi: 10.1111/j.1600-0722.2011.00895.x. Epub 2011 Dec 12.
Hertwig's epithelial root sheath (HERS), epithelial rests of Malassez (ERM) cells, and reduced ameloblasts undergo apoptosis during tooth development. This study examined the effects of dental follicle cells and cementoblasts on the apoptosis of ameloblast-lineage and HERS/ERM cells derived from the enamel organ. We also elucidated the induction pathways and identified the apoptotic pathway involved in this process. Here, we showed terminal deoxynucleotidyl transferase-mediated biotin-dUTP nick-end labeling (TUNEL)-positive HERS cells and reduced ameloblasts near dental follicle cells during tooth development. Co-culturing ameloblast-lineage cell line (ALC) ameloblasts and HERS/ERM cells with either dental follicle cells or OCCM-30 cementoblasts markedly enhanced the apoptosis of ameloblasts and HERS/ERM cells compared with cells cultured alone. However, dental follicle cells and cementoblasts did not modulate the apoptotic responses of co-cultured non-odontogenic MCF10A or KB cells. When ameloblasts + HERS and cementoblasts + dental follicle cells were co-cultured, the expression of Fas ligand (FasL) increased in cementoblasts + dental follicle cells, while the expression of Fas increased in ameloblasts + HERS. Interestingly, recombinant FasL induced ameloblast apoptosis while the cementoblast-induced ameloblast apoptosis was suppressed by the Fas/FasL antagonist Kp7-6. These results suggest that during tooth development, dental follicle cells and cementoblasts induce apoptosis of ameloblast-lineage and HERS/ERM cells through the Fas-FasL pathway, but do not induce the apoptosis of non-odontogenic epithelial cells.
赫特维希上皮根鞘（HERS）、马拉瑟上皮剩余（ERM）细胞和成釉细胞在牙齿发育过程中会发生凋亡。本研究检测了牙囊细胞和成牙骨质细胞对来自牙釉质器官的成釉细胞系及HERS/ERM细胞凋亡的影响。我们还阐明了诱导途径，并确定了该过程中涉及的凋亡途径。在此，我们发现牙齿发育过程中，在牙囊细胞附近存在末端脱氧核苷酸转移酶介导的生物素-dUTP缺口末端标记（TUNEL）阳性的HERS细胞和成釉细胞。与单独培养的细胞相比，将成釉细胞系细胞系（ALC）成釉细胞和HERS/ERM细胞与牙囊细胞或OCCM-30成牙骨质细胞共培养，显著增强了成釉细胞和HERS/ERM细胞的凋亡。然而，牙囊细胞和成牙骨质细胞并未调节共培养的非牙源性MCF10A或KB细胞的凋亡反应。当成釉细胞+HERS与成牙骨质细胞+牙囊细胞共培养时，成牙骨质细胞+牙囊细胞中Fas配体（FasL）的表达增加，而成釉细胞+HERS中Fas的表达增加。有趣的是，重组FasL诱导成釉细胞凋亡，而Fas/FasL拮抗剂Kp7-6抑制了成牙骨质细胞诱导的成釉细胞凋亡。这些结果表明，在牙齿发育过程中，牙囊细胞和成牙骨质细胞通过Fas-FasL途径诱导成釉细胞系及HERS/ERM细胞凋亡，但不诱导非牙源性上皮细胞凋亡。
