{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T17:39:37Z","timestamp":1768585177423,"version":"3.49.0"},"reference-count":45,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2023,12,17]],"date-time":"2023-12-17T00:00:00Z","timestamp":1702771200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea NRF funded by the Ministry of Education","doi-asserted-by":"publisher","award":["NRF-2020R1I1A2073643"],"award-info":[{"award-number":["NRF-2020R1I1A2073643"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea NRF funded by the Ministry of Education","doi-asserted-by":"publisher","award":["NRF-2021R1A2C1005280"],"award-info":[{"award-number":["NRF-2021R1A2C1005280"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"Korean government (MSIT)","doi-asserted-by":"publisher","award":["NRF-2020R1I1A2073643"],"award-info":[{"award-number":["NRF-2020R1I1A2073643"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"Korean government (MSIT)","doi-asserted-by":"publisher","award":["NRF-2021R1A2C1005280"],"award-info":[{"award-number":["NRF-2021R1A2C1005280"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Adipose-derived mesenchymal stem cells (ASCs) have the potential to differentiate into bone, cartilage, fat, and neural cells and promote tissue regeneration and healing. It is known that they can have variable responses to hypoxic conditions. In the present study, we aimed to explore diverse changes in the cells and secretome of ASCs under a hypoxic environment over time and to present the possibility of ASCs as therapeutic agents from a different perspective. The expression differences of proteins between normoxic and hypoxic conditions (6, 12, or 24 h) were specifically investigated in human ASCs using 2-DE combined with MALDI-TOF MS analysis, and secreted proteins in ASC-derived conditioned media (ASC-derived CM) were examined by an adipokine array. In addition, genetic and\/or proteomic interactions were assessed using a DAVID and miRNet functional annotation bioinformatics analysis. We found that 64 and 5 proteins were differentially expressed in hypoxic ASCs and in hypoxic ASC-derived CM, respectively. Moreover, 7 proteins among the 64 markedly changed spots in hypoxic ASCs were associated with bone-related diseases. We found that two proteins, cathepsin D (CTSD) and cathepsin L (CTSL), identified through an adipokine array independently exhibited significant efficacy in promoting osteocyte differentiation in bone-marrow-derived mesenchymal stem cells (BM-MSCs). This finding introduces a promising avenue for utilizing hypoxia-preconditioned ASC-derived CM as a potential therapeutic approach for bone-related diseases.<\/jats:p>","DOI":"10.3390\/cells12242852","type":"journal-article","created":{"date-parts":[[2023,12,18]],"date-time":"2023-12-18T05:41:35Z","timestamp":1702878095000},"page":"2852","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Enhanced Osteocyte Differentiation: Cathepsin D and L Secretion by Human Adipose-Derived Mesenchymal Stem Cells"],"prefix":"10.3390","volume":"12","author":[{"given":"Jung-Won","family":"Choi","sequence":"first","affiliation":[{"name":"Medical Science Research Institute, College of Medicine, Catholic Kwandong University, Incheon Metropolitan City 22711, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9814-0682","authenticated-orcid":false,"given":"Soyeon","family":"Lim","sequence":"additional","affiliation":[{"name":"Department of Convergence Science, College of Medicine, Catholic Kwandong University, Incheon Metropolitan City 22711, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5143-703X","authenticated-orcid":false,"given":"Seung Eun","family":"Jung","sequence":"additional","affiliation":[{"name":"Medical Science Research Institute, College of Medicine, Catholic Kwandong University, Incheon Metropolitan City 22711, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9705-531X","authenticated-orcid":false,"given":"Seongtae","family":"Jeong","sequence":"additional","affiliation":[{"name":"The Interdisciplinary Graduate Program in Integrative Biotechnology, Yonsei University, Seoul 03722, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hanbyeol","family":"Moon","sequence":"additional","affiliation":[{"name":"Department of Integrated Omics for Biomedical Sciences, Graduate School, Yonsei University, Seoul 03722, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9962-0941","authenticated-orcid":false,"given":"Byeong-Wook","family":"Song","sequence":"additional","affiliation":[{"name":"Department of Convergence Science, College of Medicine, Catholic Kwandong University, Incheon Metropolitan City 22711, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Il-Kwon","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Convergence Science, College of Medicine, Catholic Kwandong University, Incheon Metropolitan City 22711, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Seahyoung","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Convergence Science, College of Medicine, Catholic Kwandong University, Incheon Metropolitan City 22711, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ki-Chul","family":"Hwang","sequence":"additional","affiliation":[{"name":"Department of Convergence Science, College of Medicine, Catholic Kwandong University, Incheon Metropolitan City 22711, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3144-4822","authenticated-orcid":false,"given":"Sang Woo","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Convergence Science, College of Medicine, Catholic Kwandong University, Incheon Metropolitan City 22711, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,12,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1186\/s13287-019-1165-5","article-title":"Stem cells: Past, present, and future","volume":"10","author":"Zakrzewski","year":"2019","journal-title":"Stem Cell Res. 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