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bioRxiv · 10.1101/184523

Protective effect of estrogen against intervertebral disc degeneration is attenuated by miR-221 through targeting estrogen receptor

Sheng, B.·Yuan, Y.·Liu, X.·Zhang, Y.·Liu, H.·Shen, X.·Liu, B.·Chang, L.
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Abstract

Intervertebral disc degeneration (IDD) is a multifactorial disease that associates apoptosis, senescence and calcification of cartilage cells, inflammatory response and alterations in the extracellular matrix. Previous documents imply that estrogen and miR-221 may be involved in IDD. This study further investigated their regulatory mechanisms underlying IDD. Normal and degenerated cartilaginous endplates (CEP) tissues were isolated surgically from juvenile patients with idiopathic scoliosis and adult patients with IDD, respectively. PCR and western blot assays showed decreased aggrecan, Col2A1, TGF-{beta} and estrogen receptor (ER) levels in CEP, but increased MMP-3, adamts-5, IL-1{beta}, TNF-, IL-6 and miR-221 levels. CEP cells were harvested from degenerated CEP tissues and treated with doses of 17{beta}-E2. 17{beta}-E2 increased expression of aggrecan and Col2A1 levels in endplate chondrocytes and secretion of TGF-{beta}, but decreased IL-6 secretion. Moreover, 17{beta}-E2 inhibited the apoptosis and cell-cycle arrest in G0/G1, improving the cell viability. These data indicated estrogen confers protective effect against IDD. However, we found that ER was a target of miR-221 via luciferase assay. miR-221 up-regulation via the mimics or ER knockdown attenuated these protective effects conferred by estrogen, while intervention of miR-221 via the inhibitors promoted the protective effects. This study provided novel evidence that estrogen confers protective effects of CEP against IDD, however, up-regulated miR-221 in degenerated CEP decreased the protective effects via targeting ER, thus it may be an important cause for IDD.

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Sheng, B., Yuan, Y., Liu, X., Zhang, Y., Liu, H., Shen, X., Liu, B., Chang, L.. 2017-09-05. Protective effect of estrogen against intervertebral disc degeneration is attenuated by miR-221 through targeting estrogen receptor. https://doi.org/10.1101/184523

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