Department of Orthopaedic Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Department of Anaesthesia and Intensive Care, The Chinese University of Hong Kong, Hong Kong, China.
J Pineal Res. 2017 Oct;63(3). doi: 10.1111/jpi.12435. Epub 2017 Aug 16.
Pinealectomy in vertebrates accelerated intervertebral disk degeneration (IDD). However, the potential mechanisms, particularly melatonin's role, are still to be clarified. In this study, for first time, melatonin membrane receptors of MT1 and MT2 were found to be present in the human intervertebral disk tissues and nucleus pulposus (NP) cells, respectively. Melatonin treatment significantly inhibited NP cell proliferation in dose-dependent manner. Accordingly, melatonin down-regulated gene expression of cyclin D1, PCNA, matrix metallopeptidase-3, and matrix metallopeptidase-9 and upregulated gene expression of collagen type II alpha 1 chain and aggrecan in NP cells. These effects of melatonin were blocked by luzindole, a nonspecific melatonin membrane receptor antagonist. Signaling pathway analysis indicated that in the intervertebral disk tissues and NP cells, melatonin acted on MT1/2 and subsequently reduced phosphorylation of phosphoinositide 3-kinase p85 regulatory subunit, phosphoinositide-dependent kinase-1, and Akt. The results indicate that melatonin is a crucial regulator of NP cell function and plays a vital role in prevention of IDD.
脊椎动物的松果体切除术加速了椎间盘退行性变（IDD）。然而，其潜在机制，特别是褪黑素的作用，仍有待阐明。在这项研究中，褪黑素膜受体 MT1 和 MT2 首次被发现在人类椎间盘组织和髓核（NP）细胞中分别存在。褪黑素处理以剂量依赖性方式显著抑制 NP 细胞增殖。相应地，褪黑素下调了 NP 细胞中环细胞周期蛋白 D1、增殖细胞核抗原、基质金属蛋白酶-3 和基质金属蛋白酶-9 的基因表达，并上调了 NP 细胞中 II 型胶原α1 链和聚集蛋白聚糖的基因表达。褪黑素的这些作用被非特异性褪黑素膜受体拮抗剂 luzindole 阻断。信号通路分析表明，在椎间盘组织和 NP 细胞中，褪黑素作用于 MT1/2，随后降低了磷酸肌醇 3-激酶 p85 调节亚基、磷酸肌醇依赖性激酶-1 和 Akt 的磷酸化。结果表明，褪黑素是 NP 细胞功能的重要调节剂，在预防 IDD 中发挥着至关重要的作用。
