Yuda Asuka, Maeda Hidefumi, Fujii Shinsuke, Monnouchi Satoshi, Yamamoto Naohide, Wada Naohisa, Koori Katsuaki, Tomokiyo Atsushi, Hamano Sayuri, Hasegawa Daigaku, Akamine Akifumi
Department of Endodontology and Operative Dentistry, Division of Oral Rehabilitation, Faculty of Dental Science, Kyushu University, Fukuoka, Japan.
J Cell Physiol. 2015 Jan;230(1):150-9. doi: 10.1002/jcp.24693.
Appropriate mechanical loading during occlusion and mastication play an important role in maintaining the homeostasis of periodontal ligament (PDL) tissue. Connective tissue growth factor (CTGF/CCN2), a matricellular protein, is known to upregulate extracellular matrix production, including collagen in PDL tissue. However, the underlying mechanisms of CTGF/CCN2 in regulation of PDL tissue integrity remain unclear. In this study, we investigated the effect of CTGF/CCN2 on osteo/cementoblastic and fibroblastic differentiation of human PDL stem cells using the cell line 1-11. CTGF/CCN2 expression in rat PDL tissue and human PDL cells (HPDLCs) was confirmed immunohisto/cytochemically. Mechanical loading was found to increase gene expression and secretion of CTGF/CCN2 in HPDLCs. CTGF/CCN2 upregulated the proliferation and migration of 1-11 cells. Furthermore, increased bone/cementum-related gene expression in this cell line led to mineralization. In addition, combined treatment of 1-11 cells with CTGF/CCN2 and transforming growth factor-β1 (TGF-β1) significantly promoted type I collagen and fibronectin expression compared with that of TGF-β1 treatment alone. Thus, these data suggest the underlying biphasic effects of CTGF/CCN2 in 1-11 cells, inducible osteo/cementoblastic, and fibroblastic differentiation dependent on the environmental condition. CTGF/CCN2 may contribute to preservation of the structural integrity of PDL tissue, implying its potential use as a therapeutic agent for PDL regeneration.
咬合和咀嚼过程中的适当机械负荷在维持牙周膜（PDL）组织的稳态中起着重要作用。结缔组织生长因子（CTGF/CCN2）是一种基质细胞蛋白，已知其可上调细胞外基质的产生，包括PDL组织中的胶原蛋白。然而，CTGF/CCN2调节PDL组织完整性的潜在机制仍不清楚。在本研究中，我们使用1-11细胞系研究了CTGF/CCN2对人PDL干细胞成骨/成牙骨质细胞和成纤维细胞分化的影响。通过免疫组织化学/细胞化学方法证实了大鼠PDL组织和人PDL细胞（HPDLCs）中CTGF/CCN2的表达。发现机械负荷可增加HPDLCs中CTGF/CCN2的基因表达和分泌。CTGF/CCN2上调了1-11细胞的增殖和迁移。此外，该细胞系中骨/牙骨质相关基因表达的增加导致了矿化。此外，与单独使用转化生长因子-β1（TGF-β1）处理相比，用CTGF/CCN2和TGF-β1联合处理1-11细胞显著促进了I型胶原蛋白和纤连蛋白的表达。因此，这些数据表明CTGF/CCN2在1-11细胞中具有潜在的双相作用，可诱导成骨/成牙骨质细胞和成纤维细胞分化，这取决于环境条件。CTGF/CCN2可能有助于维持PDL组织的结构完整性，这意味着它有可能用作PDL再生的治疗剂。
