Santos de Araujo Rui M, Oba Yasuo, Moriyama Keiji
Department of Orthodontics and Dentofacial Orthopedics, Institute of Health Biosciences, The University of Tokushima Graduate School, 3-18-15 Kuramoto-cho, Tokushima 770-8504, Japan.
Cell Biochem Funct. 2007 Nov-Dec;25(6):753-8. doi: 10.1002/cbf.1400.
Mechanical stress is thought to regulate the expression of genes in the periodontal ligament (PDL) cells. Using a microarray approach, we recently identified a regulator of G-protein signaling 2 (RGS2) as an up-regulated gene in the PDL cells under compressive force. The RGS protein family is known to turn off G-protein signaling. G-protein signaling involves the production of cAMP, which is thought to be one of the biological mediators in response to mechanical stress. Here, we investigated the role of RGS2 in the PDL cells under mechanical stress. PDL cells derived from the ligament tissues of human premolar teeth were cultured in collagen gels and subjected to static compressive force. Compressive force application time-dependently enhanced RGS2 expression and intracellular cAMP levels. To examine the interrelationship between RGS2 and cAMP, the PDL cells were treated with 2',5'-dideoxyadenosine (DDA), an inhibitor of adenyl cyclase, or antisense S-oligonucleotide (S-ODN) to RGS2 under compressive force. DDA dose-dependently inhibited RGS2 stimulated by compressive force. Blockage of RGS2 by antisense S-ODN elevated the cAMP levels compared with controls. These results indicate that cAMP stimulates RGS2 expression, which in turn leads to a decrease in the cAMP production by inactivating the G-protein signaling in the mechanically stressed PDL cells.
机械应力被认为可调节牙周膜(PDL)细胞中基因的表达。我们最近采用微阵列方法,确定了G蛋白信号调节因子2(RGS2)是受压PDL细胞中上调的基因。已知RGS蛋白家族可关闭G蛋白信号。G蛋白信号涉及cAMP的产生,而cAMP被认为是响应机械应力的生物介质之一。在此,我们研究了RGS2在机械应力下PDL细胞中的作用。将源自人类前磨牙韧带组织的PDL细胞培养于胶原凝胶中,并施加静态压力。施加压力的时间依赖性地增强了RGS2的表达和细胞内cAMP水平。为了研究RGS2与cAMP之间的相互关系,在受压情况下,用腺苷酸环化酶抑制剂2',5'-二脱氧腺苷(DDA)或针对RGS2的反义S-寡核苷酸(S-ODN)处理PDL细胞。DDA剂量依赖性地抑制受压刺激的RGS2。与对照相比,反义S-ODN阻断RGS2可提高cAMP水平。这些结果表明,cAMP刺激RGS2表达,进而通过使机械应力下的PDL细胞中的G蛋白信号失活导致cAMP产生减少。