{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T13:27:36Z","timestamp":1790515656408,"version":"4.1.0"},"reference-count":48,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2022,3,29]],"date-time":"2022-03-29T00:00:00Z","timestamp":1648512000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Romanian Ministry of Education and Research, CCCDI - UEFISCDI","award":["PN-III-P2-2.1-PED-2019-4906"],"award-info":[{"award-number":["PN-III-P2-2.1-PED-2019-4906"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Parathyroid hormone (PTH) is a key regulator of calcium, phosphate and vitamin D metabolism. Although it has been reported that aortic valve calcification was positively associated with PTH, the pathophysiological mechanisms and the direct effects of PTH on human valvular cells remain unclear. Here we investigated if PTH induces human valvular endothelial cells (VEC) dysfunction that in turn could impact the switch of valvular interstitial cells (VIC) to an osteoblastic phenotype. Human VEC exposed to PTH were analyzed by qPCR, western blot, Seahorse, ELISA and immunofluorescence. Our results showed that exposure of VEC to PTH affects VEC metabolism and functions, modifications that were accompanied by the activation of p38MAPK and ERK1\/2 signaling pathways and by an increased expression of osteogenic molecules (BMP-2, BSP, osteocalcin and Runx2). The impact of dysfunctional VEC on VIC was investigated by exposure of VIC to VEC secretome, and the results showed that VIC upregulate molecules associated with osteogenesis (BMP-2\/4, osteocalcin and TGF-\u03b21) and downregulate collagen I and III. In summary, our data show that PTH induces VEC dysfunction, which further stimulates VIC to differentiate into a pro-osteogenic pathological phenotype related to the calcification process. These findings shed light on the mechanisms by which PTH participates in valve calcification pathology and suggests that PTH and the treatment of hyperparathyroidism represent a therapeutic strategy to reduce valvular calcification.<\/jats:p>","DOI":"10.3390\/ijms23073776","type":"journal-article","created":{"date-parts":[[2022,3,29]],"date-time":"2022-03-29T21:44:52Z","timestamp":1648590292000},"page":"3776","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Parathyroid Hormone Induces Human Valvular Endothelial Cells Dysfunction That Impacts the Osteogenic Phenotype of Valvular Interstitial Cells"],"prefix":"10.3390","volume":"23","author":[{"given":"Mihaela","family":"Vadana","sequence":"first","affiliation":[{"name":"Biopathology and Therapy of Inflammation, Institute of Cellular Biology and Pathology \u201cNicolae Simionescu\u201d, 050568 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sergiu","family":"Cecoltan","sequence":"additional","affiliation":[{"name":"Biopathology and Therapy of Inflammation, Institute of Cellular Biology and Pathology \u201cNicolae Simionescu\u201d, 050568 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Letitia","family":"Ciortan","sequence":"additional","affiliation":[{"name":"Biopathology and Therapy of Inflammation, Institute of Cellular Biology and Pathology \u201cNicolae Simionescu\u201d, 050568 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1957-3752","authenticated-orcid":false,"given":"Razvan D.","family":"Macarie","sequence":"additional","affiliation":[{"name":"Biopathology and Therapy of Inflammation, Institute of Cellular Biology and Pathology \u201cNicolae Simionescu\u201d, 050568 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreea C.","family":"Mihaila","sequence":"additional","affiliation":[{"name":"Biopathology and Therapy of Inflammation, Institute of Cellular Biology and Pathology \u201cNicolae Simionescu\u201d, 050568 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monica M.","family":"Tucureanu","sequence":"additional","affiliation":[{"name":"Biopathology and Therapy of Inflammation, Institute of Cellular Biology and Pathology \u201cNicolae Simionescu\u201d, 050568 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana-Maria","family":"Gan","sequence":"additional","affiliation":[{"name":"Biopathology and Therapy of Inflammation, Institute of Cellular Biology and Pathology \u201cNicolae Simionescu\u201d, 050568 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maya","family":"Simionescu","sequence":"additional","affiliation":[{"name":"Biopathology and Therapy of Inflammation, Institute of Cellular Biology and Pathology \u201cNicolae Simionescu\u201d, 050568 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8079-4191","authenticated-orcid":false,"given":"Ileana","family":"Manduteanu","sequence":"additional","affiliation":[{"name":"Biopathology and Therapy of Inflammation, Institute of Cellular Biology and Pathology \u201cNicolae Simionescu\u201d, 050568 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ionel","family":"Droc","sequence":"additional","affiliation":[{"name":"Cardiovascular Surgery Department, Central Military Hospital, 010825 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5748-5641","authenticated-orcid":false,"given":"Elena","family":"Butoi","sequence":"additional","affiliation":[{"name":"Biopathology and Therapy of Inflammation, Institute of Cellular Biology and Pathology \u201cNicolae Simionescu\u201d, 050568 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,3,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1262","DOI":"10.1038\/sj.ki.5002241","article-title":"Vascular calcification: Contribution of parathyroid hormone in renal failure","volume":"71","author":"Neves","year":"2007","journal-title":"Kidney Int."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1016\/S0140-6736(09)60507-9","article-title":"Hyperparathyroidism","volume":"374","author":"Fraser","year":"2009","journal-title":"Lancet"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1007\/s10157-006-0432-9","article-title":"Regulation of parathyroid function in chronic kidney disease (CKD)","volume":"10","author":"Fukagawa","year":"2006","journal-title":"Clin. 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