{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T02:40:30Z","timestamp":1791859230294,"version":"4.3.4"},"reference-count":14,"publisher":"Oxford University Press (OUP)","issue":"9","license":[{"start":{"date-parts":[[2018,1,20]],"date-time":"2018-01-20T00:00:00Z","timestamp":1516406400000},"content-version":"vor","delay-in-days":1,"URL":"https:\/\/academic.oup.com\/journals\/pages\/about_us\/legal\/notices"}],"funder":[{"DOI":"10.13039\/501100016034","name":"Fondation du Rein","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100016034","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Prix Jeune Chercheur 2013"},{"DOI":"10.13039\/501100001677","name":"INSERM","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100001677","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100006687","name":"Universit\u00e9 Claude Bernard Lyon 1","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100006687","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001665","name":"ANR","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001665","id-type":"DOI","asserted-by":"publisher"}]},{"name":"LYSBONE","award":["ANR-15-CE14-0010-01"],"award-info":[{"award-number":["ANR-15-CE14-0010-01"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2018,9,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Bone impairment is a poorly described complication of nephropathic cystinosis (NC). The objectives of this study were to evaluate in vitro effects of cystinosin (CTNS) mutations on bone resorption and of cysteamine treatment on bone cells [namely human osteoclasts (OCs) and murine osteoblasts].<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Human OCs were differentiated from peripheral blood mononuclear cells (PBMCs) of patients and healthy donors (HDs). Cells were treated with increasing doses of cysteamine in PBMCs or on mature OCs to evaluate its impact on differentiation and resorption, respectively. Similarly, cysteamine-treated osteoblasts derived from murine mesenchymal stem cells were assessed for differentiation and activity with toxicity and proliferation assays.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>CTNS was expressed in human OCs derived from HDs; its expression was regulated during monocyte colony-stimulating factor- and receptor activator of nuclear factor-\u03baB-dependent osteoclastogenesis and required for efficient bone resorption. Cysteamine had no impact on osteoclastogenesis but inhibited in vitro HD osteoclastic resorption; however, NC OC-mediated bone resorption was impaired only at high doses. Only low concentrations of cysteamine (50\u2009\u03bcM) stimulated osteoblastic differentiation and maturation, while this effect was no longer observed at higher concentrations (200\u2009\u00b5M).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>CTNS is required for proper osteoclastic activity. In vitro low doses of cysteamine have beneficial antiresorptive effects on healthy human-derived OCs and may partly correct the CTNS-induced osteoclastic dysfunction in patients with NC. Moreover, in vitro low doses of cysteamine also stimulate osteoblastic differentiation and mineralization, with an inhibitory effect at higher doses, likely explaining, at least partly, the bone toxicity observed in patients receiving high doses of cysteamine.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/ndt\/gfx362","type":"journal-article","created":{"date-parts":[[2017,12,18]],"date-time":"2017-12-18T15:23:41Z","timestamp":1513610621000},"page":"1525-1532","source":"Crossref","is-referenced-by-count":14,"title":["Bone disease in nephropathic cystinosis is related to cystinosin-induced osteoclastic dysfunction"],"prefix":"10.1093","volume":"33","author":[{"given":"Debora","family":"Claramunt-Taberner","sequence":"first","affiliation":[{"name":"Centre de R\u00e9f\u00e9rence des Maladies R\u00e9nales Rares, H\u00f4pital Femme M\u00e8re Enfant, Hospices Civils de Lyon, Bron, 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France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olivier","family":"Peyruchaud","sequence":"additional","affiliation":[{"name":"INSERM, UMR 1033, Facult\u00e9 de M\u00e9decine Lyon Est, Universit\u00e9 Claude Bernard Lyon 1, Lyon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irma","family":"Machuca-Gayet","sequence":"additional","affiliation":[{"name":"INSERM, UMR 1033, Facult\u00e9 de M\u00e9decine Lyon Est, Universit\u00e9 Claude Bernard Lyon 1, Lyon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Justine","family":"Bacchetta","sequence":"additional","affiliation":[{"name":"Centre de R\u00e9f\u00e9rence des Maladies R\u00e9nales Rares, H\u00f4pital Femme M\u00e8re Enfant, Hospices Civils de Lyon, Bron, France"},{"name":"INSERM, UMR 1033, Facult\u00e9 de M\u00e9decine Lyon Est, Universit\u00e9 Claude Bernard Lyon 1, Lyon, France"},{"name":"Universit\u00e9 de Lyon, Lyon, 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