Abstract
BackgroundEstradiol plays an important role in the regulation of collagen metabolism. Deficiency of estradiol has been reported to be associated with the degeneration of many connective tissues. However, the association of estradiol and hypertrophy of the ligamentum flavum was seldom explored. Therefore, we studied the effects of estradiol on cultured cells from the ligamentum flavum.MethodsPrimary cultures of human ligamentum flavum cells obtained from surgical specimens of 14 patients undergoing spinal surgery were used to investigate the effect of estradiol on cell proliferation and the expression of collagen, elastin, and matrix metalloproteinases. Downstream pathways of estrogen receptor underlying the regulation of metalloproteinases were also investigated.ResultsIn our study, we revealed the existence of estrogen receptors on both female and male ligamentum flavum cells with a gender difference. 17β-estradiol increased early (24 hours) proliferation of ligamentum flavum cells in a dose dependent manner and the effect could not be seen when the cell density increased. Estradiol with a concentration of 10-9 M decreased collagen levels and increased the expression of MMP-13. Adding an antagonist of PI3K downstream pathway could reverse the expression of MMP-13 caused by estradiol.ConclusionsThe results implied estradiol regulated the expression of MMP-13 via PI3K pathway and contributed to the homeostasis of extracellular matrix in the ligamentum flavum.
Highlights
Estradiol plays an important role in the regulation of collagen metabolism
We investigated the effects of estradiol on cultured human ligamentum flavum cells by examining the presence of estradiol receptors, effects of estradiol on cell proliferation, regulation of collagen and elastin metabolisms, the relationship of matrix metalloproteinases (MMPs) with estradiol treatment and the signaling mechanisms underlying it
Estrogen receptors were found on both female and male ligamentum flavum Immunohistochemistry revealed estrogen receptor-β was positively stained in both male and female LF cells with similar density, while estrogen receptor-α was identified on female LF cells with lower density and was barely seen on cells from a male patient (Figure 1)
Summary
Estradiol plays an important role in the regulation of collagen metabolism. Deficiency of estradiol has been reported to be associated with the degeneration of many connective tissues. Deficiency of estradiol has been reported to be associated with collagen metabolism and the subsequent degeneration of skin, arteries, bone and intervertebral discs [11,12,13]. To understand the equilibrium between matrix degradation and synthesis in the aging and /or degenerative ligamentum flavum, it is important to evaluate the expression and activity of MMPs. In the present work, we investigated the effects of estradiol on cultured human ligamentum flavum cells by examining the presence of estradiol receptors, effects of estradiol on cell proliferation, regulation of collagen and elastin metabolisms, the relationship of matrix metalloproteinases (MMPs) with estradiol treatment and the signaling mechanisms underlying it. The understandings of estradiol’s effects on cell proliferation and matrix metabolism of the ligamentum flavum should provide more insights into the influences of estradiol on the pathophysiology of spondylotic lumbar stenosis during aging in women
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