mechanical signaling via ion channels and neuronal transmitter-receptors

我们的研究重点是骨骼中的一种离子通道--起搏器通道(HCN)。甲型H1N1病毒位于破骨细胞分泌酸的褶皱边缘区域。为了阐明hcns的作用，我们雇佣了hcn1缺陷小鼠。1.研究了HCN3在成骨细胞中的作用：1.与野生型(WT)相比，HCN1-KO组小鼠的骨小梁质量和骨小梁数目的结构参数显著降低，而骨小梁分离度显著增加。骨形成(MAR和BFR/BS)和骨吸收(Oc.S/BS和OC.N/BS)的组织形态计量学指数增加。2：膜片钳记录显示，HCN1缺乏降低了超极化激活电流的激活率，尽管幅度与WT相同，可能是因为其他HCN亚型保持完整。3：通过转染HCN3基因过表达促进了WT成骨细胞的增殖，以细胞总数衡量。4：HCN4基因敲除后破骨细胞ih显著减少，提示HCN1-KO可能是基于细胞功能障碍而产生的破骨细胞ih。HCN1对破骨细胞的酸分泌和分化有调节作用。此外，缺乏HCN1可上调成骨细胞中HCN3的表达。HCN3可能与成骨细胞骨形成有关。

Our study focused on one of ion channels, pacemaker channel (HCN) in bone. HCN1 is localized around ruffled border area where osteoclast secretes acid. To elucidate the role of HCNs, HCN1 deficient mice were hired. The role of HCN3 in osteoblasts was investigated.1 : In HCN1-deficient mice, trabecular bone mass and the structural parameter of Trabecular Number were significantly lower, whereas Trabecular Separation was significantly higher, in HCN1-KO than in wild type (WT). Histomorphometiric indices of bone formation (MAR and BFR/BS) and resorption (Oc.S/BS and Oc.N/BS) were increased.2 : Patch clamp recordings showed that HCN1-deficiency decreased the activation rate of the hyperpolarization-activated current although the amplitude was same as WT, probably because other HCN subtypes remained intact.3 : Overexpression of HCN3 by transfecting the gene enhanced proliferation of WT-osteoblasts as measured by total cell number.4 : Osteoclastic Ih was significantly reduced by knockdown of HCN4, suggesteing that osteoclastic Ih could be generated from HCN1 and HCN4.The high bone turnover in HCN1-KO was likely to be based on cellular dysfunctions. HCN1 could modulate acid secretion and differentiation in osteoclasts. In addition, lack of HCN1 upregulated expression of HCN3 in osteoblasts. HCN3 may contribute to osteoblastic bone formation.