{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,14]],"date-time":"2026-02-14T12:39:51Z","timestamp":1771072791472,"version":"3.50.1"},"reference-count":40,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2021,9,4]],"date-time":"2021-09-04T00:00:00Z","timestamp":1630713600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Italian Ministry of Health","award":["Ricerca Corrente"],"award-info":[{"award-number":["Ricerca Corrente"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Vitamin D showed a protective effect on intervertebral disc degeneration (IDD) although conflicting evidence is reported. An explanation could be due to the presence of the FokI functional variant in the vitamin D receptor (VDR), observed as associated with spine pathologies. The present study was aimed at investigating\u2014through high-throughput gene and protein analysis\u2014the response of human disc cells to vitamin D, depending on the VDR FokI variants. The presence of FokI VDR polymorphism was determined in disc cells from patients with discopathy. 1,25(OH)2D3 was administered to the cells with or without interleukin 1 beta (IL-1\u03b2). Microarray, protein arrays, and multiplex protein analysis were performed. In both FokI genotypes (FF and Ff), vitamin D upregulated metabolic genes of collagen. In FF cells, the hormone promoted the matrix proteins synthesis and a downregulation of enzymes involved in matrix catabolism, whereas Ff cells behaved oppositely. In FF cells, inflammation seems to hamper the synthetic activity mediated by vitamin D. Angiogenic markers were upregulated in FF cells, along with hypertrophic markers, some of them upregulated also in Ff cells after vitamin D treatment. Higher inflammatory protein modulation after vitamin D treatment was observed in inflammatory condition. These findings would help to clarify the clinical potential of vitamin D supplementation in patients affected by IDD.<\/jats:p>","DOI":"10.3390\/ijms22179603","type":"journal-article","created":{"date-parts":[[2021,9,6]],"date-time":"2021-09-06T13:15:56Z","timestamp":1630934156000},"page":"9603","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["High-Throughput Gene and Protein Analysis Revealed the Response of Disc Cells to Vitamin D, Depending on the VDR FokI Variants"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1800-3424","authenticated-orcid":false,"given":"Alessandra","family":"Colombini","sequence":"first","affiliation":[{"name":"Orthopaedic Biotechnology Lab, IRCCS Istituto Ortopedico Galeazzi, 20161 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9810-8818","authenticated-orcid":false,"given":"Paola","family":"De Luca","sequence":"additional","affiliation":[{"name":"Orthopaedic Biotechnology Lab, IRCCS Istituto Ortopedico Galeazzi, 20161 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Davide","family":"Cangelosi","sequence":"additional","affiliation":[{"name":"Laboratorio di Genetica Umana, IRCCS Istituto Giannina Gaslini, 16147 Genoa, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6162-8668","authenticated-orcid":false,"given":"Carlotta","family":"Perucca Orfei","sequence":"additional","affiliation":[{"name":"Orthopaedic Biotechnology Lab, IRCCS Istituto Ortopedico Galeazzi, 20161 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0272-7417","authenticated-orcid":false,"given":"Enrico","family":"Ragni","sequence":"additional","affiliation":[{"name":"Orthopaedic Biotechnology Lab, IRCCS Istituto Ortopedico Galeazzi, 20161 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6463-6564","authenticated-orcid":false,"given":"Marco","family":"Vigan\u00f2","sequence":"additional","affiliation":[{"name":"Orthopaedic Biotechnology Lab, IRCCS Istituto Ortopedico Galeazzi, 20161 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michela","family":"Malacarne","sequence":"additional","affiliation":[{"name":"Laboratorio di Genetica Umana, IRCCS Istituto Giannina Gaslini, 16147 Genoa, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8052-9515","authenticated-orcid":false,"given":"Mauro","family":"Castagnetta","sequence":"additional","affiliation":[{"name":"Laboratorio di Istocompatibilit\u00e0\/IBMDR, Ospedali Galliera, 16128 Genoa, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marco","family":"Brayda-Bruno","sequence":"additional","affiliation":[{"name":"Scoliosis Unit, Department of Orthopedics and Traumatology-Spine Surgery III, IRCCS Istituto Ortopedico Galeazzi, 20161 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8440-865X","authenticated-orcid":false,"given":"Domenico","family":"Coviello","sequence":"additional","affiliation":[{"name":"Laboratorio di Genetica Umana, IRCCS Istituto Giannina Gaslini, 16147 Genoa, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9979-3092","authenticated-orcid":false,"given":"Laura","family":"de Girolamo","sequence":"additional","affiliation":[{"name":"Orthopaedic Biotechnology Lab, IRCCS Istituto Ortopedico Galeazzi, 20161 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,9,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2347","DOI":"10.1007\/s00198-014-2749-7","article-title":"Skeletal and nonskeletal effects of vitamin D: Is vitamin D a tonic for bone and other tissues?","volume":"25","author":"Reid","year":"2014","journal-title":"Osteoporos. 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