The role of gap junctions in megakaryocyte-mediated osteoblast proliferation and differentiation.
The role of gap junctions in megakaryocyte-mediated osteoblast proliferation and differentiation.
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DOI：
10.1016/j.bone.2008.08.117
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发表时间：
2009-01
期刊：
影响因子：
4.1
通讯作者：
Kacena, Melissa A.
中科院分区：
文献类型：
--
作者：
Ciovacco, Wendy A.;Goldberg, Carolyn G.;Taylor, Amanda F.;Lemieux, Justin M.;Horowitz, Mark C.;Donahue, Henry J.;Kacena, Melissa A.
缝隙连接(GJS)是一种跨膜通道，通过允许小的信号分子(如钙离子、肌醇磷酸盐和环核苷酸)在细胞之间传递，促进细胞间的通讯。在过去的二十年里，许多研究描述了GJ细胞间通讯(GJIC)在包括骨细胞在内的许多细胞的增殖和分化中的作用。最近，我们报道了巨核细胞通过旁分泌信号机制促进成骨细胞(OB)的增殖。在这里，我们确定该响应是否由GJIC促成。首先，我们证明MKs表达连接蛋白43(Cx43)，这是包括OBS在内的骨细胞表达的主要GJ蛋白。接下来，我们提供的数据表明，MKs可以通过GJIC与OBS进行通信，并且两种不同的GJ解偶联剂18α-甘草次酸(αGA)或油酰胺的加入抑制了这种通信。然后我们证明了抑制MK介导的GJIC进一步增强了MK刺激OB增殖的能力。最后，我们发现，虽然与OBS一起培养MK可以减少几种分化标志物/基质蛋白(I型胶原、骨钙素和碱性磷酸酶)的基因表达，降低碱性磷酸酶的活性，并减少OBS中的矿化，但阻断GJIC并不会导致MK诱导的OB基因表达、酶水平或矿化结节形成的减少。总体而言，这些数据提供了证据，证明MK-OB细胞和OB细胞之间的GJIC是起作用的，与类似处理的OB细胞相比，抑制MK-OB细胞培养中的GJIC可以促进OB细胞的增殖，而不会明显改变分化。因此，这些关于MK-OB GJIC抑制的观察可能为合成代谢骨形成的潜在新靶点提供洞察力。
Gap junctions (GJs) are membrane-spanning channels that facilitate intercellular communication by allowing small signaling molecules (e.g. calcium ions, inositol phosphates, and cyclic nucleotides) to pass from cell to cell. Over the past two decades, many studies have described a role for GJ intercellular communication (GJIC) in the proliferation and differentiation of many cells, including bone cells. Recently, we reported that megakaryocytes (MKs) enhance osteoblast (OB) proliferation by a juxtacrine signaling mechanism. Here we determine whether that response is facilitated by GJIC. First we demonstrate that MKs express connexin 43 (Cx43), the predominant GJ protein expressed by bone cells, including OBs. Next, we provide data showing that MKs can communicate with OBs via GJIC, and that the addition of two distinct GJ uncouplers, 18α-glycyrrhetinic acid (αGA) or oleamide, inhibits this communication. We then demonstrate that inhibiting MK-mediated GJIC further enhances the ability of MK to stimulate OB proliferation. Finally, we show that while culturing MKs with OBs reduces gene expression of several differentiation markers/matrix proteins (type I collagen, osteocalcin, and alkaline phosphatase), reduces alkaline phosphatase enzymatic activity, and decreases mineralization in OBs, blocking GJIC does not result in MK-induced reductions in OB gene expression, enzymatic levels, or mineralized nodule formation. Overall, these data provide evidence that GJIC between MKs and OBs is functional, and that inhibiting GJIC in MK-OB cultures enhances OB proliferation without apparently altering differentiation when compared to similarly treated OB cultures. Thus, these observations regarding MK-OB GJIC inhibition may provide insight regarding potential novel targets for anabolic bone formation.
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DOI：
10.1016/s0006-291x(03)00502-3
发表时间：
2003-04-18
影响因子：
3.1
作者：
Ransjö, M;Sahli, J;Lie, A
通讯作者：
Lie, A
DOI：
10.1152/ajpcell.2000.278.2.c315
发表时间：
2000-02-01
影响因子：
5.5
作者：
Donahue, HJ;Li, ZY;Yellowley, CE
通讯作者：
Yellowley, CE
影响因子：
4.1
作者：
Schiller, PC;D'Ippolito, G;Howard, GA
通讯作者：
Howard, GA
影响因子：
5.3
作者：
CENTRELLA, M;MCCARTHY, TL;CANALIS, E
通讯作者：
CANALIS, E
影响因子：
4.1
作者：
Schiller, PC;D'ippolito, G;Howard, GA
通讯作者：
Howard, GA