Metabolic effects of vitamin D active metabolites in monolayer and micromass cultures of nucleus pulposus and annulus fibrosus cells isolated from human intervertebral disc

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• 作者：Alessandra Colombini^a ; ^{alessandra.colombini@grupposandonato.it} ; Patrizia Lanteri^a ; Giovanni Lombardi^a ; Dalila Grasso^a ; Camilla Recordati^b ; Alessio Lovi^a ; Giuseppe Banfi^a ; ^c ; Roberto Bassani^a ; Marco Brayda-Bruno^a
• 关键词：Intervertebral disc cells ; Vitamin D receptor ; 1 ; 25(OH)2D3 ; Proliferation ; Matrix genes expression
• 刊名：The International Journal of Biochemistry and Cell Biology
• 出版年：2012
• 期刊代码：127_13572725
• 类别：med
• 出版时间：June, 2012
• 卷：44
• 期：6
• 页码：1019-1030
• 文件大小：2765 K

摘要

Intragenic polymorphisms in the vitamin D receptor gene are linked to disc degeneration features, suggesting that alterations in the vitamer-mediated signalling could be involved in the pathophysiology of the disc and that interaction of disc cells with vitamin D metabolites may be critical for disc health.

The vitamer-mediated modulation of disc cells proliferation, metabolic activity, extracellular matrix (ECM) genes expression and proteins production was investigated.

It was stated that disc cells express vitamin D receptor and are very sensitive to metabolic stimuli.

In monolayer cultures, 1,25(OH)₂D₃, but not 24,25(OH)₂D₃, determined an inhibition of the proliferation and regulated also the ECM genes expression in nucleus pulposus and annulus fibrosus cells.

Micromass cultures induced a more physiologic expression pattern of extracellular matrix genes. Cells Treatment with vitamin D metabolites did not result in relevant modifications of glycosaminoglycans production, except for annulus cells, whose production was reduced after 1,25(OH)₂D₃ treatment. Moreover, a reduced glycosaminoglycans staining in both cell types and a significant reduced aggrecan gene expression in annulus cells treated with 1,25(OH)₂D₃ were observed. A reduction of collagen I and II staining in annulus cells 1,25(OH)₂D₃ treated, in accordance with a downregulation of collagen genes expression, was also registered.

Finally, the vitamin D receptor gene expression did not show significant metabolite-mediated modification in monolayer or micromass cultures.

These findings could enhance new insights on the biochemical mechanisms regulated by vitamin D in disc cartilage and possibly involved in the development of physiological/pathological modifications of the disc.