{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T04:53:41Z","timestamp":1791262421450,"version":"4.1.0"},"reference-count":32,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2015,2,18]],"date-time":"2015-02-18T00:00:00Z","timestamp":1424217600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Italian Ministry of Education, University and Research","award":["2006062453_002"],"award-info":[{"award-number":["2006062453_002"]}]},{"DOI":"10.13039\/501100003500","name":"University of Padua","doi-asserted-by":"crossref","award":["CPDA085494"],"award-info":[{"award-number":["CPDA085494"]}],"id":[{"id":"10.13039\/501100003500","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Cellular Molecular Medi"],"published-print":{"date-parts":[[2015,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Medullary nephrocalcinosis is a hallmark of medullary sponge kidney (<jats:styled-content style=\"fixed-case\">MSK<\/jats:styled-content>). We had the opportunity to study a spontaneous calcification process <jats:italic>in vitro<\/jats:italic> by utilizing the renal cells of a patient with <jats:styled-content style=\"fixed-case\">MSK<\/jats:styled-content> who was heterozygous for the c.\u201027 + 18G&gt;A variant in the <jats:styled-content style=\"fixed-case\">GDNF<\/jats:styled-content> gene encoding glial cell\u2010derived neurotrophic factor. The cells were obtained by collagenase digestion of papillary tissues from the <jats:styled-content style=\"fixed-case\">MSK<\/jats:styled-content> patient and from two patients who had no <jats:styled-content style=\"fixed-case\">MSK<\/jats:styled-content> or nephrocalcinosis. These cells were typed by immunocytochemistry, and the presence of mineral deposits was studied using von Kossa staining, scanning electron microscopy analysis and an <jats:styled-content style=\"fixed-case\">ALP<\/jats:styled-content> assay. Osteoblastic lineage markers were studied using immunocytochemistry and <jats:styled-content style=\"fixed-case\">RT<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">PCR<\/jats:styled-content>. Staminality markers were also analysed using flow cytometry, magnetic cell separation technology, immunocytochemistry and <jats:styled-content style=\"fixed-case\">RT<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">PCR<\/jats:styled-content>. Starting from p2, <jats:styled-content style=\"fixed-case\">MSK<\/jats:styled-content> and control cells formed nodules with a behaviour similar to that of calcifying pericytes; however, <jats:styled-content style=\"fixed-case\"><jats:roman>Ca<jats:sub>2<\/jats:sub>PO<jats:sub>4<\/jats:sub><\/jats:roman><\/jats:styled-content> was only found in the <jats:styled-content style=\"fixed-case\">MSK<\/jats:styled-content> cultures. The <jats:styled-content style=\"fixed-case\">MSK<\/jats:styled-content> cells had morphologies and immunophenotypes resembling those of pericytes or stromal stem cells and were positive for vimentin, <jats:styled-content style=\"fixed-case\">ZO<\/jats:styled-content>1, \u03b1<jats:styled-content style=\"fixed-case\">SMA<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>146. In addition, the <jats:styled-content style=\"fixed-case\">MSK<\/jats:styled-content> cells expressed osteocalcin and osteonectin, indicating an osteoblast\u2010like phenotype. In contrast to the control cells, <jats:styled-content style=\"fixed-case\">GDNF<\/jats:styled-content> was down\u2010regulated in the <jats:styled-content style=\"fixed-case\">MSK<\/jats:styled-content> cells. Stable <jats:styled-content style=\"fixed-case\">GDNF<\/jats:styled-content> knockdown was established in the <jats:styled-content style=\"fixed-case\">HK<\/jats:styled-content>2 cell line and was found to promote <jats:styled-content style=\"fixed-case\"><jats:roman>Ca<jats:sub>2<\/jats:sub>PO<jats:sub>4<\/jats:sub><\/jats:roman><\/jats:styled-content> deposition when the cells were incubated with calcifying medium by regulating the osteonectin\/osteopontin ratio in favour of osteonectin. Our data indicate that the human papilla may be a perivascular niche in which pericyte\/stromal\u2010like cells can undergo osteogenic differentiation under particular conditions and suggest that <jats:styled-content style=\"fixed-case\">GDNF<\/jats:styled-content> down\u2010regulation may have influenced the observed phenomenon.<\/jats:p>","DOI":"10.1111\/jcmm.12514","type":"journal-article","created":{"date-parts":[[2015,2,18]],"date-time":"2015-02-18T10:45:09Z","timestamp":1424256309000},"page":"889-902","source":"Crossref","is-referenced-by-count":25,"title":["Spontaneous calcification process in primary renal cells from a medullary sponge kidney patient harbouring a <scp>GDNF<\/scp> mutation"],"prefix":"10.1111","volume":"19","author":[{"given":"Federica","family":"Mezzabotta","sequence":"first","affiliation":[{"name":"Laboratory of Histomorphology and Molecular Biology of the Kidney Nephrology Division Department of Medicine DIMED University of Padua Padua 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