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Melatonin inhibits nucleus pulposus ( NP ) cell proliferation and extracellular matrix ( ECM ) remodeling via the melatonin membrane receptors mediated PI 3K‐Akt pathway
Author(s) -
Li Zheng,
Li Xingye,
Chen Chong,
Chan Matthew T. V.,
Wu William Ka Kei,
Shen Jianxiong
Publication year - 2017
Publication title -
journal of pineal research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.881
H-Index - 131
eISSN - 1600-079X
pISSN - 0742-3098
DOI - 10.1111/jpi.12435
Subject(s) - melatonin , luzindole , microbiology and biotechnology , melatonin receptor , signal transduction , receptor , cell growth , biology , chemistry , medicine , endocrinology , biochemistry
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 MT 1 and MT 2 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 MT 1/2 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 .