{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T03:12:43Z","timestamp":1790651563775,"version":"4.1.0"},"reference-count":43,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2021,12,11]],"date-time":"2021-12-11T00:00:00Z","timestamp":1639180800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003196","name":"Ministero della Salute","doi-asserted-by":"publisher","award":["GR-2016-02363570"],"award-info":[{"award-number":["GR-2016-02363570"]}],"id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"publisher"}]},{"name":"AISS","award":["Grant 2018"],"award-info":[{"award-number":["Grant 2018"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Shwachman\u2013Diamond syndrome (SDS) is a rare autosomal recessive disorder characterized by bone marrow failure, exocrine pancreatic insufficiency, and skeletal abnormalities, caused by loss-of-function mutations in the SBDS gene, a factor involved in ribosome biogenesis. By analyzing osteoblasts from SDS patients (SDS-OBs), we show that SDS-OBs displayed reduced SBDS gene expression and reduced\/undetectable SBDS protein compared to osteoblasts from healthy subjects (H-OBs). SDS-OBs cultured in an osteogenic medium displayed a lower mineralization capacity compared to H-OBs. Whole transcriptome analysis showed significant differences in the gene expression of SDS-OBs vs. H-OBs, particularly in the ossification pathway. SDS-OBs expressed lower levels of the main genes responsible for osteoblastogenesis. Of all downregulated genes, Western blot analyses confirmed lower levels of alkaline phosphatase and collagen type I in SDS-OBs than in H-OBs. Interestingly, SDS-OBs showed higher protein levels of p53, an inhibitor of osteogenesis, compared to H-OBs. Silencing of Tp53 was associated with higher collagen type I and alkaline phosphatase protein levels and an increase in SDS-OB mineralization capacity. In conclusion, our results show that the reduced capacity of SDS-OBs to mineralize is mediated, at least in part, by the high levels of p53 and highlight an important role of SBDS in osteoblast functions.<\/jats:p>","DOI":"10.3390\/ijms222413331","type":"journal-article","created":{"date-parts":[[2021,12,13]],"date-time":"2021-12-13T01:28:11Z","timestamp":1639358891000},"page":"13331","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Enhanced p53 Levels Are Involved in the Reduced Mineralization Capacity of Osteoblasts Derived from Shwachman\u2013Diamond Syndrome Subjects"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1166-3091","authenticated-orcid":false,"given":"Annalisa","family":"Frattini","sequence":"first","affiliation":[{"name":"Institute for Genetic and Biomedical Research (IRGB), UOS Milano CNR, Via Fantoli, 15\/16, 20138 Milano, Italy"},{"name":"Department of Medicine and Surgery (DMC), Universita\u2019 degli Studi dell\u2019Insubria, Via J.H. Dunant, 5, 21100 Varese, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8940-8859","authenticated-orcid":false,"given":"Simona","family":"Bolamperti","sequence":"additional","affiliation":[{"name":"Bone Metabolism Unit, IRCCS Ospedale San Raffaele, Via Olgettina, 60, 20132 Milano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3209-8917","authenticated-orcid":false,"given":"Roberto","family":"Valli","sequence":"additional","affiliation":[{"name":"Department of Medicine and Surgery (DMC), Universita\u2019 degli Studi dell\u2019Insubria, Via J.H. 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Dunant, 5, 21100 Varese, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdul Waheed","family":"Khan","sequence":"additional","affiliation":[{"name":"Department of Medicine and Surgery (DMC), Universita\u2019 degli Studi dell\u2019Insubria, Via J.H. Dunant, 5, 21100 Varese, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1736-0531","authenticated-orcid":false,"given":"Alessandro","family":"Rubinacci","sequence":"additional","affiliation":[{"name":"Bone Metabolism Unit, IRCCS Ospedale San Raffaele, Via Olgettina, 60, 20132 Milano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3732-4725","authenticated-orcid":false,"given":"Isabella","family":"Villa","sequence":"additional","affiliation":[{"name":"Bone Metabolism Unit, IRCCS Ospedale San Raffaele, Via Olgettina, 60, 20132 Milano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,12,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"645","DOI":"10.1016\/S0022-3476(64)80150-5","article-title":"The syndrome of pancreatic insufficiency and bone marrow dysfunction","volume":"65","author":"Shwachman","year":"1964","journal-title":"J. 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