The role of the ERK1/2 pathway as an alternative to the aging-diminished cyclic AMP pathway in calcitonin-mediated chondrogenesis in human nucleus pulposus
The role of the ERK1/2 pathway as an alternative to the aging-diminished cyclic AMP pathway in calcitonin-mediated chondrogenesis in human nucleus pulposus
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DOI：
10.1016/j.biomaterials.2012.06.088
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发表时间：
2012-11-01
期刊：
影响因子：
14
通讯作者：
Deng, Win-Ping
中科院分区：
文献类型：
--
作者：
Chen, Wei-Hong;Zeng, Rong;Deng, Win-Ping
由髓中央核(HNP)老化引起的人类椎间盘退行性变是一个不可逆转的过程，其恢复已成为严重的问题。本研究探讨了降钙素促进HNP再生的相关机制，以及降钙素对HNP增龄性改变的影响。将收获的HNP群体命名为YHNP(来自50岁的年轻供者)。原代OhNP细胞比YhNP细胞表现出更多的肥大表型。然而，降钙素(10(-8)-10(-6)M)通过上调软骨形成特异性基因和蛋白的表达，在YhNP和OhNP中诱导了相同的软骨形成。经降钙素处理后，细胞存活率增加。降钙素受体(CTR)在YhNP和OhNP细胞中的表达差异无统计学意义。有趣的是，在降钙素诱导的软骨形成途径中，在降钙素治疗后的YhNP中检测到高度增加的cAMP(CAMP)，但在OhNP中随着年龄的增长而显著减少。然而，为了维持软骨的形成，降钙素在两个细胞中都诱导了磷酸化的ERK1/2(p-ERK)。PD98059抑制ERK1/2后，降钙素诱导的软骨形成几乎被抑制，而YhNP细胞不受影响。我们的结果表明，降钙素在HNP上的再生随着年龄的增长而保持，这是通过另一条信号通路来满足的。因此，降钙素在临床治疗椎间盘再生方面显示出巨大的潜力，而不需要考虑衰老。(C)爱思唯尔有限公司出版的2012年。
Human disc degeneration initiated by aging in the central nucleus pulposus (hNP) is an irreversible process and the recovery has become seriously emerging. In this study, the related mechanisms of calcitonin on the regeneration of hNP and the effects of calcitonin on the age-related alterations were examined. The harvested hNP population was designated as YhNP (from young donor, age 50). Primary OhNP cells showed more hypertrophic phenotypes than YhNP. However, calcitonin (10(-8)-10(-6) M) was able to induce the same chondrogenesis in both YhNP and OhNP by elevating chondrogenic specific-mRNA and protein expressions. Their cell viabilities were increased with calcitonin treatment. No significant differences of calcitonin receptor (CTR) were expressed between YhNP and OhNP cells. Interestingly, in calcitonin-induced pathways for chondrogenesis, highly increased cyclic AMP (cAMP) was detected in YhNP but was strongly diminished by aging in OhNP after calcitonin treatment. However, to maintain the chondrogenesis, calcitonin-induced an alterative phosphorylated ERK1/2 (p-ERK) in both cells. After inhibiting ERK1/2 by PD98059, calcitonin-induced chondrogenesis in OhNP was almost restrained while YhNP cells were not affected. Our results demonstrated that the regeneration of calcitonin on hNP was maintained with aging which was satisfied by an alternative signaling pathway. Therefore, calcitonin shows great potential for clinical therapy for disc regeneration without aging considerations. (C) 2012 Published by Elsevier Ltd.