State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China.
Sci Rep. 2018 Oct 4;8(1):14792. doi: 10.1038/s41598-018-33247-8.
It is well recognized that osteocytes communicate with each other via gap junctions and that connxin43 (Cx43) shows its great potential in gap junction for the contribution enabling transmission of small molecules and operating in an autocrine/a paracrine manner. Fibroblast growth factors (FGFs) play significant roles in new bone formation and adult bone remodeling, and FGF signaling is regulated by the precise spatiotemporal approaches. However, the influence of FGF7 on osteocyte cell processes is not well elucidated. In this study, we aimed to examine the impact of FGF7 on osteocyte cell processes by characterizing the expression of Cx43 and to reveal the underlying mechanism regulating this cell process. We first found that the mRNA level of FGF7 was higher relative to other FGF family members both in osteocytes cell line (MLO-Y4) and bone tissue. We then demonstrated that FGF7 could increase the expression of Cx43 in osteocytes and promote the cell processes in the form of gap junctions between osteocytes. This modulation was due to the FGF7-induced cytoplasmic accumulation and resultant nuclear translocation of β-catenin. Our results could help us to further understand the importance of FGF7 on bone cell behavior and bone physiology and even pathology.
人们普遍认识到，骨细胞通过缝隙连接相互通讯，连接蛋白 43（Cx43）在缝隙连接中具有很大的潜力，能够传递小分子并以自分泌/旁分泌的方式发挥作用。成纤维细胞生长因子（FGFs）在新骨形成和成人骨重塑中发挥重要作用，FGF 信号受精确的时空调控。然而，FGF7 对骨细胞过程的影响尚未得到充分阐明。在这项研究中，我们旨在通过研究 Cx43 的表达来研究 FGF7 对骨细胞过程的影响，并揭示调节该细胞过程的潜在机制。我们首先发现，在成骨细胞系（MLO-Y4）和骨组织中，FGF7 的 mRNA 水平相对于其他 FGF 家族成员更高。然后，我们证明 FGF7 可以增加骨细胞中 Cx43 的表达，并通过骨细胞之间的缝隙连接促进细胞过程。这种调节是由于 FGF7 诱导的β-连环蛋白的细胞质积累和随后的核转位。我们的结果可以帮助我们进一步了解 FGF7 对骨细胞行为和骨生理学甚至病理学的重要性。
