{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,3]],"date-time":"2026-04-03T18:07:13Z","timestamp":1775239633685,"version":"3.50.1"},"reference-count":37,"publisher":"Public Library of Science (PLoS)","issue":"4","license":[{"start":{"date-parts":[[2026,4,3]],"date-time":"2026-04-03T00:00:00Z","timestamp":1775174400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100021171","name":"Basic and Applied Basic Research Foundation of Guangdong Province","doi-asserted-by":"publisher","award":["2021A1515110647"],"award-info":[{"award-number":["2021A1515110647"]}],"id":[{"id":"10.13039\/501100021171","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Guangzhou Science and Technology Project","award":["202201020256"],"award-info":[{"award-number":["202201020256"]}]},{"name":"Guangzhou Science and Technology Project","award":["2024A04J3855"],"award-info":[{"award-number":["2024A04J3855"]}]},{"DOI":"10.13039\/501100010883","name":"Traditional Chinese Medicine Bureau of Guangdong Province","doi-asserted-by":"publisher","award":["20251103"],"award-info":[{"award-number":["20251103"]}],"id":[{"id":"10.13039\/501100010883","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:sec id=\"sec001\">\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>It has been demonstrated that both hUCMSC-exo and Cyasterone exhibit protective effects against steroid-induced osteonecrosis of the femoral head (SIONFH). Additionally, studies have shown that CTSD N-glycosylation influences BMSC apoptosis. Based on these findings, we aim to investigate the mechanism of hUCMSCs-exo@Cyasterone in the Dex-induced BMSCs model of SIONFH, focusing on its regulatory role in CTSD N-glycosylation during apoptosis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec002\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      The SIONFH cell model was induced by dexamethasone (Dex) at a concentration of 10\n                      <jats:sup>-6<\/jats:sup>\n                      mol\/L. Experiments with hUMSCs-exo@Cyasterone and CTSD mutants were performed in the BMSC model to analyze proliferation, apoptosis, lysosomal pH, lysosomal membrane permeability, and lysosomal colocalization. Additionally, the expression of apoptosis-related proteins in BMSCs and CTSD in lysosomes and the cytoplasm were examined.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec003\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>MTT, AO staining, EDU staining, flow cytometry, and confocal microscopy revealed that hUMSCs-exo@Cyasterone attenuated the proliferation of Dex-induced BMSCs and reduced the lysosomal membrane permeability. It also decreased the expression level of apoptosis-related proteins including BID, Caspase-3, and Caspase-1, as well as the levels of CTSD in lysosomal and cytoplasm. CTSD-N258A inhibited BMSC apoptosis, enhanced the protective effect of hUMSCs-exo@Cyasterone, and promoted the lysosomal localization of CTSD and the lysosomal membrane permeability. Moreover, CTSD-N258A helped suppress the expression of apoptosis-related proteins and reduced CTSD expression in cytoplasm and lysosomes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec004\">\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>hUMSCs-exo@Cyasterone mitigates apoptosis in Dex-induced BMSCs, a cell model of steroid-induced femoral head necrosis, by modulating the N-glycosylation modification of CTSD-N258A.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1371\/journal.pone.0337562","type":"journal-article","created":{"date-parts":[[2026,4,3]],"date-time":"2026-04-03T17:35:38Z","timestamp":1775237738000},"page":"e0337562","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["hUMSCs-exo@Cyasterone protects the cell model of steroid-induced femur head necrosis by regulating N-glycosylation modification of 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