Functions of beta2‐adrenergic receptor in human periodontal ligament cells
Functions of beta2‐adrenergic receptor in human periodontal ligament cells
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人牙周膜细胞中β2肾上腺素受体的功能
DOI：
10.1002/jcb.29706
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发表时间：
2020
影响因子：
4
通讯作者：
Maeda Hidefumi
中科院分区：
文献类型：
--
作者：
Hamano Sayuri;Tomokiyo Atsushi;Hasegawa Daigaku;Yuda Asuka;Sugii Hideki;Yoshida Shinichiro;Mitarai Hiromi;Wada Naohisa;Maeda Hidefumi
肾上腺素能受体是去甲肾上腺素和肾上腺素的受体，有九种不同的亚型。尤其是β-2肾上腺素能受体(β2-AR)与骨和心脏组织内稳态的恢复和维持有关，但β2-AR信号在牙周膜组织中的功能作用尚未得到充分研究。本研究探讨了β-2-AR在人牙周膜样变组织中的表达及其在细胞中的表达特征。β-2-AR在大鼠牙周膜组织和人牙周膜细胞(HPDLCs-2G和-3S)中表达。咬合负荷组β-2-AR高表达，未负荷组表达下调。在HPDLC中，β-2-AR的表达在拉伸负荷下增加。研究高表达β-2-AR的PDL克隆细胞(2-23细胞)中PDL相关分子的基因表达。用特异性β2-AR激动剂非诺特罗(Fenoterol，Fen)处理HPDLCs，观察其基因表达和细胞内环磷酸腺苷(CAMP)水平。在2~23细胞中，β2-AR的过表达显著促进了相关分子的基因表达。Fen诱导HPDLCs中PDL相关分子表达上调，细胞内cAMP水平升高。在两种HPDLC中，用蛋白激酶A抑制剂抑制cAMP信号转导可抑制FEN诱导的α-平滑肌肌动蛋白基因表达。结果提示，咬合力对牙周膜组织中β2-AR的表达有重要影响，β2-AR参与牙周膜细胞成纤维细胞分化和胶原合成。通过β-2-AR传递的信号可能对PDL组织的修复和动态平衡起重要作用。
Adrenergic receptors (ARs) are receptors of noradrenalin and adrenalin, of which there are nine different subtypes. In particular, β2 adrenergic receptor (β2‐AR) is known to be related to the restoration and maintenance of homeostasis in bone and cardiac tissues; however, the functional role of signaling through β2‐AR in periodontal ligament (PDL) tissue has not been fully examined. In this report, we investigated that β2‐AR expression in PDL tissues and their features in PDL cells. β2‐AR expressed in rat PDL tissues and human PDL cells (HPDLCs) derived from two different patients (HPDLCs‐2G and ‐3S). Rat PDL tissue with occlusal loading showed high β2‐AR expression, while its expression was downregulated in that without loading. In HPDLCs,β2‐ARexpression was increased exposed to stretch loading. The gene expression of PDL‐related molecules was investigated in PDL clone cells (2‐23 cells) overexpressing β2‐AR. Their gene expression and intracellular cyclic adenosine monophosphate (cAMP) levels were also investigated in HPDLCs treated with a specific β2‐AR agonist, fenoterol (FEN). Overexpression of β2‐AR significantly promoted the gene expression of PDL‐related molecules in 2 to 23 cells. FEN led to an upregulation in the expression of PDL‐related molecules and increased intracellular cAMP levels in HPDLCs. In both HPDLCs, inhibition of cAMP signaling by using protein kinase A inhibitor suppressed the FEN‐induced gene expression of α‐smooth muscle actin. Our findings suggest that the occlusal force is important for β2‐AR expression in PDL tissue and β2‐AR is involved in fibroblastic differentiation and collagen synthesis of PDL cells. The signaling through β2‐AR might be important for restoration and homeostasis of PDL tissue.