{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,18]],"date-time":"2026-10-18T08:55:14Z","timestamp":1792313714170,"version":"4.4.0"},"reference-count":20,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2025,4,2]],"date-time":"2025-04-02T00:00:00Z","timestamp":1743552000000},"content-version":"vor","delay-in-days":1,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100020884","name":"Agencia Nacional de Investigaci\u00f3n y Desarrollo","doi-asserted-by":"publisher","award":["11190426"],"award-info":[{"award-number":["11190426"]}],"id":[{"id":"10.13039\/501100020884","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["acrjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["ACR Open Rheumatology"],"published-print":{"date-parts":[[2025,4]]},"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>We aimed to assess whether the presence of radiographically confirmed calcinosis of the hands in patients with systemic sclerosis (SSc) is associated with increased osteoclastogenesis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We recruited 20 patients with SSc (10 with calcinosis and 10 without calcinosis) and 10 age\u2010 and gender\u2010matched healthy controls. Hand radiographs were scored using the validated Scleroderma Clinical Trials Consortium (SCTC) radiographic severity score for calcinosis. To evaluate osteoclastogenesis, peripheral blood mononuclear cells (PBMCs) were cultured with RANKL and macrophage colony\u2010stimulating factor; osteoclasts were identified using tartrate\u2010resistant acid phosphatase staining. Measures of bone resorption (RANKL, osteoprotegerin [OPG]) and ischemia or endothelial function (vascular endothelial growth factor, angiopoietin\u20101, and angiopoietin\u20102 [Ang\u20102]) were also evaluated.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Patients with SSc were all women and Hispanic, and the majority (n = 12, 60%) had limited SSc skin type. Mean \u00b1 SD age was 55.2 \u00b1 14.8 years; mean \u00b1 SD disease duration was 9.5 \u00b1 6.5 years from first non\u2010Raynaud phenomenon symptom. Patients with SSc with calcinosis had more digital ischemia than patients without calcinosis. Median SCTC score in patients with SSc with calcinosis was 11.1 (range 0.7\u2013286). After 9 days in culture, PBMCs from patients with calcinosis originated a significantly higher number of osteoclasts (33.0 \u00b1 20.3 cells\/well) than patients without calcinosis (15.3 \u00b1 6.9 cells\/well) and healthy individuals (11.2 \u00b1 2.6 cells\/well) (\n                      <jats:italic>P<\/jats:italic>\n                      = 0.001). The severity of calcinosis was not correlated with the number of osteoclasts per well (r = 0.27,\n                      <jats:italic>P<\/jats:italic>\n                      = 0.5); however, it was correlated with RANKL (r = 0.82,\n                      <jats:italic>P<\/jats:italic>\n                      = 0.004), RANKL\/OPG ratio (r = 0.86,\n                      <jats:italic>P<\/jats:italic>\n                      = 0.002), and Ang\u20102 levels (r = 0.86,\n                      <jats:italic>P<\/jats:italic>\n                      = 0.002).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Calcinosis in patients with SSc is associated with an increased propensity of peripheral blood cells to form osteoclasts. Targeted inhibition of osteoclastogenesis may provide a specific therapeutic option for patients with SSc\u2010associated calcinosis.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/acr2.70029","type":"journal-article","created":{"date-parts":[[2025,4,4]],"date-time":"2025-04-04T14:26:25Z","timestamp":1743776785000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Osteoclastogenesis in Patients With Systemic Sclerosis With and Without Calcinosis Cutis"],"prefix":"10.1002","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3357-9402","authenticated-orcid":false,"given":"Antonia","family":"Valenzuela","sequence":"first","affiliation":[{"name":"Pontificia Universidad Cat\u00f3lica de Chile  Santiago Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guillermo","family":"P\u00e9rez","sequence":"additional","affiliation":[{"name":"Pontificia Universidad Cat\u00f3lica de Chile  Santiago Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorinda","family":"Chung","sequence":"additional","affiliation":[{"name":"Stanford University School of Medicine  Palo Alto California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Felipe","family":"S\u00e1nchez","sequence":"additional","affiliation":[{"name":"Pontificia Universidad Cat\u00f3lica de Chile  Santiago Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carolina","family":"Iturriaga","sequence":"additional","affiliation":[{"name":"Pontificia Universidad Cat\u00f3lica de Chile  Santiago Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebeca","family":"Montalva","sequence":"additional","affiliation":[{"name":"Pontificia Universidad Cat\u00f3lica de Chile  Santiago Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7904-262X","authenticated-orcid":false,"given":"Arturo","family":"Borzutzky","sequence":"additional","affiliation":[{"name":"Pontificia Universidad Cat\u00f3lica de Chile  Santiago Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,4,2]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.semarthrit.2020.06.007"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1097\/BOR.0000000000000539"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.semarthrit.2016.05.008"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/kei277"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/kep151"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.39424"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1210\/endo.142.12.8536"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.humpath.2005.10.007"},{"issue":"7","key":"e_1_2_6_10_1","first-page":"1529","article-title":"Elevated vascular endothelial growth factor in systemic sclerosis","volume":"30","author":"Choi JJ","year":"2003","journal-title":"J Rheumatol"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10456-009-9147-3"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.38098"},{"issue":"3","key":"e_1_2_6_13_1","first-page":"158","article-title":"Systemic sclerosis related calcinosis: patients provide what specialists want to learn","volume":"167","author":"Christensen A","year":"2015","journal-title":"J La State Med 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