Bone tissue homeostasis relies upon the ability of cells to detect and interpret extracellular signals that direct changes in tissue architecture. This study utilized a four-point bending model to create both fluid shear and strain forces (loading) during the time-dependent progression of MC3T3-E1 preosteoblasts along the osteogenic lineage. Loading was shown to increase cell number, alkaline phosphatase (ALP) activity, collagen synthesis, and the mRNA expression levels of Runx2, osteocalcin (OC), osteopontin, and cyclo-oxygenase-2. However, mineralization in these cultures was inhibited, despite an increase in calcium accumulation, suggesting that loading may inhibit mineralization in order to increase matrix deposition. Loading also increased fibroblast growth factor receptor-3 (FGFR3) expression coincident with an inhibition of FGFR1, FGFR4, FGF1, and extracellular signal-related kinase (ERK)1/2 phosphorylation. To examine whether these loading-induced changes in cell phenotype and FGFR expression could be attributed to the inhibition of ERK1/2 phosphorylation, cells were grown for 25 days in the presence of the MEK1/2 inhibitor, U0126. Significant increases in the expression of FGFR3, ALP, and OC were observed, as well as the inhibition of FGFR1, FGFR4, and FGF1. However, U0126 also increased matrix mineralization, demonstrating that inhibition of ERK1/2 phosphorylation cannot fully account for the changes observed in response to loading. In conclusion, this study demonstrates that preosteoblasts are mechanoresponsive, and that long-term loading, whilst increasing proliferation and differentiation of preosteoblasts, inhibits matrix mineralization. In addition, the increase in FGFR3 expression suggests that it may have a role in osteoblast differentiation.

译文

骨组织稳态依赖于细胞检测和解释引导组织结构变化的细胞外信号的能力。这项研究利用四点弯曲模型在MC3T3-E1前成骨细胞沿成骨谱系的时间依赖性过程中产生流体剪切力和应变力 (载荷)。负载被证明可以增加细胞数量,碱性磷酸酶 (ALP) 活性,胶原蛋白合成以及Runx2,骨钙素 (OC),骨桥蛋白和cyclo-oxygenase-2的mRNA表达水平。然而,尽管钙积累增加,但这些培养物中的矿化仍受到抑制,这表明负载可能会抑制矿化以增加基质沉积。负载也增加了成纤维细胞生长因子受体3 (FGFR3) 表达,同时抑制了FGFR1,FGFR4,FGF1和细胞外信号相关激酶 (ERK)1/2磷酸化。为了检查这些负载诱导的细胞表型和FGFR表达的变化是否可以归因于对ERK1/2磷酸化的抑制,在MEK1/2抑制剂u0126存在下使细胞生长25天。观察到FGFR3,ALP和OC的表达显着增加,以及对FGFR1,FGFR4和fgf1的抑制。然而,U0126也增加了基质矿化,表明对ERK1/2磷酸化的抑制不能完全解释响应负载而观察到的变化。总之,这项研究表明,前成骨细胞具有机械反应能力,并且长期负荷在增加前成骨细胞增殖和分化的同时,会抑制基质矿化。此外,FGFR3表达的增加表明它可能在成骨细胞分化中起作用。

+1
+2
100研值 100研值 ¥99课程
检索文献一次
下载文献一次

去下载>

成功解锁2个技能,为你点赞

《SCI写作十大必备语法》
解决你的SCI语法难题!

技能熟练度+1

视频课《玩转文献检索》
让你成为检索达人!

恭喜完成新手挑战

手机微信扫一扫,添加好友领取

免费领《Endnote文献管理工具+教程》

微信扫码, 免费领取

手机登录

获取验证码
登录