Sugii Hideki, Maeda Hidefumi, Tomokiyo Atsushi, Yamamoto Naohide, Wada Naohisa, Koori Katsuaki, Hasegawa Daigaku, Hamano Sayuri, Yuda Asuka, Monnouchi Satoshi, Akamine Akifumi
Department of Endodontology and Operative Dentistry, Faculty of Dental Science, Kyushu University, Higashi-ku, Fukuoka 812-8582, Japan.
Department of Endodontology, Kyushu University Hospital, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
Bone. 2014 Sep;66:62-71. doi: 10.1016/j.bone.2014.05.021. Epub 2014 Jun 10.
Periodontal ligament (PDL) tissue plays an important role in tooth preservation by structurally maintaining the connection between the tooth root and the bone. The mechanisms involved in the healing and regeneration of damaged PDL tissue, caused by bacterial infection, caries and trauma, have been explored. Accumulating evidence suggests that Activin A, a member of the transforming growth factor-β (TGF-β) superfamily and a dimer of inhibinβa, contributes to tissue healing through cell proliferation, migration, and differentiation of various target cells. In bone, Activin A has been shown to exert an inhibitory effect on osteoblast maturation and mineralization. However, there have been no reports examining the expression and function of Activin A in human PDL cells (HPDLCs). Thus, we aimed to investigate the biological effects of Activin A on HPDLCs. Activin A was observed to be localized in HPDLCs and rat PDL tissue. When PDL tissue was surgically damaged, Activin A and IL-1β expression increased and the two proteins were shown to be co-localized around the lesion. HPDLCs treated with IL-1β or TNF-α also up-regulated the expression of the gene encoding inhibinβa. Activin A promoted chemotaxis, migration and proliferation of HPDLCs, and caused an increase in fibroblastic differentiation of these cells while down-regulating their osteoblastic differentiation. These osteoblastic inhibitory effects of Activin A, however, were only noted during the early phase of HPDLC osteoblastic differentiation, with later exposures having no effect on differentiation. Collectively, our results suggest that Activin A could be used as a therapeutic agent for healing and regenerating PDL tissue in response to disease, trauma or surgical reconstruction.
牙周韧带（PDL）组织通过在结构上维持牙根与骨骼之间的连接，在牙齿保存中发挥着重要作用。人们已经对由细菌感染、龋齿和创伤引起的受损PDL组织的愈合和再生机制进行了探索。越来越多的证据表明，激活素A是转化生长因子-β（TGF-β）超家族的成员，是抑制素βa的二聚体，它通过各种靶细胞的增殖、迁移和分化促进组织愈合。在骨骼中，激活素A已被证明对成骨细胞的成熟和矿化具有抑制作用。然而，目前尚无关于激活素A在人牙周韧带细胞（HPDLCs）中的表达和功能的报道。因此，我们旨在研究激活素A对HPDLCs的生物学作用。观察到激活素A定位于HPDLCs和大鼠PDL组织中。当PDL组织受到手术损伤时，激活素A和白细胞介素-1β（IL-1β）的表达增加，并且这两种蛋白在损伤部位周围共定位。用IL-1β或肿瘤坏死因子-α（TNF-α）处理的HPDLCs也上调了编码抑制素βa的基因的表达。激活素A促进了HPDLCs的趋化性、迁移和增殖，并导致这些细胞的成纤维细胞分化增加，同时下调其成骨细胞分化。然而，激活素A的这些成骨细胞抑制作用仅在HPDLCs成骨细胞分化的早期阶段被观察到，后期暴露对分化没有影响。总的来说，我们的结果表明，激活素A可作为一种治疗剂，用于响应疾病、创伤或手术重建而愈合和再生PDL组织。
