Activation of α2A-adrenergic signal transduction in chondrocytes promotes degenerative remodelling of temporomandibular joint.
Activation of α2A-adrenergic signal transduction in chondrocytes promotes degenerative remodelling of temporomandibular joint.
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DOI：
10.1038/srep30085
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发表时间：
2016-07-25
影响因子：
4.6
通讯作者：
Wang MQ
中科院分区：
文献类型：
--
作者：
Jiao K;Zeng G;Niu LN;Yang HX;Ren GT;Xu XY;Li FF;Tay FR;Wang MQ
这项研究测试了软骨细胞中肾上腺素受体的激活是否在TMJ退行性重塑中起作用，并确定相关的机制。建立单侧前牙反牙合(UAC)大鼠TMJ退变模型。将生理盐水、α-2和β-受体拮抗剂或激动剂局部注射到UAC大鼠的TMJ区。观察软骨退变、软骨下骨微结构及软骨细胞肾上腺素受体、聚集蛋白、基质金属蛋白酶(MMPs)和RANKL的表达。用去甲肾上腺素刺激软骨细胞，研究肾上腺素受体的信号转导。关节突关节软骨α2A受体表达增加，伴有软骨退变和软骨下骨丢失。去甲肾上腺素通过ERK1/2和蛋白激酶A途径抑制软骨细胞侵袭素的表达，但刺激软骨细胞产生基质金属蛋白酶-3、基质金属蛋白酶-13和RANK1，这些作用可被α2A受体拮抗剂所阻断。此外，抑制MMP2A型肾上腺素能受体抑制软骨和软骨下退行性重塑，表现为软骨厚度增加，蛋白多糖和蛋白多糖表达增加，软骨α-3、MMP13和RANKL表达减少，骨密度、Bv/Tv增加，软骨下骨中Tb.Sp降低。相反，α2A-肾上腺素受体的激活加剧了UAC大鼠上述退行性改变。结论：软骨细胞中α2A-肾上腺素能信号的激活通过软骨细胞介导的促分解代谢活动促进了关节退行性重塑。
This study tested whether activation of adrenoreceptors in chondrocytes has roles in degenerative remodelling of temporomandibular joint (TMJ) and to determine associated mechanisms. Unilateral anterior crossbite (UAC) was established to induce TMJ degeneration in rats. Saline vehicle, α2- and β-adrenoreceptor antagonists or agonists were injected locally into the TMJ area of UAC rats. Cartilage degeneration, subchondral bone microarchitecture and the expression of adrenoreceptors, aggrecans, matrix metalloproteinases (MMPs) and RANKL by chondrocytes were evaluated. Chondrocytes were stimulated by norepinephrine to investigate signal transduction of adrenoreceptors. Increased α2A-adrenoreceptor expression was observed in condylar cartilage of UAC rats, together with cartilage degeneration and subchondral bone loss. Norepinephrine depresses aggrecans expression but stimulates MMP-3, MMP-13 and RANKL production by chondrocytes through ERK1/2 and PKA pathway; these effects were abolished by an α2A-adrenoreceptor antagonist. Furthermore, inhibition of α2A-adrenoreceptor attenuated degenerative remodelling in the condylar cartilage and subchondral bone, as revealed by increased cartilage thickness, proteoglycans and aggrecan expression, and decreased MMP-3, MMP-13 and RANKL expressions in cartilage, increased BMD, BV/TV, and decreased Tb.Sp in subchondral bone. Conversely, activation of α2A-adrenoreceptor intensified aforementioned degenerative changes in UAC rats. It is concluded that activation of α2A-adrenergic signal in chondrocytes promotes TMJ degenerative remodelling by chondrocyte-mediated pro-catabolic activities.