{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,6]],"date-time":"2026-11-06T11:32:45Z","timestamp":1793964765893,"version":"4.8.0"},"reference-count":37,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,3,30]],"date-time":"2026-03-30T00:00:00Z","timestamp":1774828800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T00:00:00Z","timestamp":1774915200000},"content-version":"vor","delay-in-days":1,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"funder":[{"name":"the Ministry of Education, Republic of Indonesia, for the Kolaborasi Penelitian Strategis (KATALIS) research grant in 2024","award":["3762\/UN1\/DITLIT\/PT.01.03\/2024"],"award-info":[{"award-number":["3762\/UN1\/DITLIT\/PT.01.03\/2024"]}]},{"name":"the Ministry of Education, Republic of Indonesia, for the Kolaborasi Penelitian Strategis (KATALIS) research grant in 2024","award":["3762\/UN1\/DITLIT\/PT.01.03\/2024"],"award-info":[{"award-number":["3762\/UN1\/DITLIT\/PT.01.03\/2024"]}]},{"name":"the Ministry of Education, Republic of Indonesia, for the Kolaborasi Penelitian Strategis (KATALIS) research grant in 2024","award":["3762\/UN1\/DITLIT\/PT.01.03\/2024"],"award-info":[{"award-number":["3762\/UN1\/DITLIT\/PT.01.03\/2024"]}]},{"name":"the Ministry of Education, Republic of Indonesia, for the Kolaborasi Penelitian Strategis (KATALIS) research grant in 2024","award":["3762\/UN1\/DITLIT\/PT.01.03\/2024"],"award-info":[{"award-number":["3762\/UN1\/DITLIT\/PT.01.03\/2024"]}]},{"name":"the Ministry of Education, Republic of Indonesia, for the Kolaborasi Penelitian Strategis (KATALIS) research grant in 2024","award":["3762\/UN1\/DITLIT\/PT.01.03\/2024"],"award-info":[{"award-number":["3762\/UN1\/DITLIT\/PT.01.03\/2024"]}]},{"name":"the Ministry of Education, Republic of Indonesia, for the Kolaborasi Penelitian Strategis (KATALIS) research grant in 2024","award":["3762\/UN1\/DITLIT\/PT.01.03\/2024"],"award-info":[{"award-number":["3762\/UN1\/DITLIT\/PT.01.03\/2024"]}]},{"name":"the Ministry of Education, Republic of Indonesia, for the Kolaborasi Penelitian Strategis (KATALIS) research grant in 2024","award":["3762\/UN1\/DITLIT\/PT.01.03\/2024"],"award-info":[{"award-number":["3762\/UN1\/DITLIT\/PT.01.03\/2024"]}]},{"name":"the Ministry of Education, Republic of Indonesia, for the Kolaborasi Penelitian Strategis (KATALIS) research grant in 2024","award":["3762\/UN1\/DITLIT\/PT.01.03\/2024"],"award-info":[{"award-number":["3762\/UN1\/DITLIT\/PT.01.03\/2024"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"DOI":"10.1038\/s41598-026-46778-2","type":"journal-article","created":{"date-parts":[[2026,3,30]],"date-time":"2026-03-30T04:34:49Z","timestamp":1774845289000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Propolis nanoemulsion and mesenchymal stem cell conditioned medium promote osteoblastogenesis against lipopolysaccharide-induced osteolysis in hyperglycemic rats"],"prefix":"10.1038","volume":"16","author":[{"given":"Ananto Ali","family":"Alhasyimi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander Patera","family":"Nugraha","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cendrawasih Andusyana","family":"Farmasyanti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Niswati Fathmah","family":"Rosyida","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hendri","family":"Susanto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muh. Ade","family":"Artasasta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Putri Cahaya","family":"Situmorang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Khairul Anuar","family":"Shariff","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,3,30]]},"reference":[{"key":"46778_CR1","doi-asserted-by":"publisher","first-page":"4482","DOI":"10.7150\/ijbs.72487","volume":"18","author":"F Jin","year":"2022","unstructured":"Jin, F. et al. Babam2 negatively regulates osteoclastogenesis by interacting with Hey1 to inhibit Nfatc1 transcription. Int J. Biol. Sci. 18, 4482\u20134496 (2022).","journal-title":"Int J. Biol. Sci"},{"key":"46778_CR2","doi-asserted-by":"publisher","first-page":"112","DOI":"10.1111\/ocr.12224","volume":"21","author":"AA Alhasyimi","year":"2018","unstructured":"Alhasyimi, A. A. et al. Enhancement of post-orthodontic tooth stability by carbonated hydroxyapatite-incorporated advanced platelet-rich fibrin in rabbits. Orthod. Craniofac. Res. 21, 112\u2013118 (2018).","journal-title":"Orthod. Craniofac. Res."},{"key":"46778_CR3","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1186\/s13287-016-0276-5","volume":"7","author":"F Loi","year":"2016","unstructured":"Loi, F. et al. The effects of immunomodulation by macrophage subsets on osteogenesis in vitro. Stem cell. Res. Ther. 7, 15 (2016).","journal-title":"Stem cell. Res. Ther."},{"key":"46778_CR4","doi-asserted-by":"publisher","first-page":"426","DOI":"10.1302\/2046-3758.117.BJR-2021-0594.R1","volume":"11","author":"P Luo","year":"2022","unstructured":"Luo, P. et al. Immunomodulatory role of T helper cells in rheumatoid arthritis: a comprehensive research review. Bone Jt. Res. 11, 426\u2013438 (2022).","journal-title":"Bone Jt. Res."},{"key":"46778_CR5","doi-asserted-by":"publisher","first-page":"137","DOI":"10.1007\/s10238-010-0117-2","volume":"11","author":"N Maruotti","year":"2011","unstructured":"Maruotti, N. et al. Osteoclastogenesis and arthritis. Clin. Exp. Med. 11, 137\u2013145 (2011).","journal-title":"Clin. Exp. Med."},{"key":"46778_CR6","doi-asserted-by":"publisher","first-page":"198","DOI":"10.1002\/jbmr.4740","volume":"38","author":"KN Bott","year":"2023","unstructured":"Bott, K. N. et al. Lipopolysaccharide-induced bone loss in rodent models: a systematic review and meta-analysis. J. Bone Min. Res. 38, 198\u2013213 (2023).","journal-title":"J. Bone Min. Res."},{"key":"46778_CR7","doi-asserted-by":"publisher","first-page":"e28435","DOI":"10.1016\/j.heliyon.2024.e28435","volume":"10","author":"D Han","year":"2024","unstructured":"Han, D. et al. Microbiota metabolites in bone: shaping health and confronting disease. Heliyon 10, e28435 (2024).","journal-title":"Heliyon"},{"key":"46778_CR8","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1016\/j.bja.2019.03.040","volume":"123","author":"J Iida","year":"2019","unstructured":"Iida, J. et al. Hyperglycaemia augments lipopolysaccharide-induced reduction in rat and human macrophage phagocytosis via the endoplasmic stress-C\/EBP homologous protein pathway. Br. J. Anaesth. 123, 51\u201359 (2019).","journal-title":"Br. J. Anaesth."},{"key":"46778_CR9","doi-asserted-by":"publisher","first-page":"198","DOI":"10.1002\/jbmr.4740","volume":"38","author":"KN Bott","year":"2023","unstructured":"Bott, K. N. et al. Lipopolysaccharide-induced bone loss in rodent models: a systematic review and meta-analysis. J. Bone Min. Res. 38, 198\u2013213 (2023).","journal-title":"J. Bone Min. Res."},{"key":"46778_CR10","doi-asserted-by":"publisher","first-page":"576","DOI":"10.1016\/j.jobcr.2025.03.013","volume":"15","author":"NR Amalia","year":"2025","unstructured":"Amalia, N. R. et al. Propolis nanoemulsion extract from celebes stingless bee (Tetragonula biroi) phytochemistry and antibacterial analysis to periodontopathogen bacteria. J. Oral Biol. Craniofac. Res. 15, 576\u2013584 (2025).","journal-title":"J. Oral Biol. Craniofac. Res."},{"key":"46778_CR11","doi-asserted-by":"crossref","unstructured":"Yosri, N. et al. R., Anti-viral and immunomodulatory properties of propolis: chemical diversity, pharmacological properties, preclinical and clinical applications, and in silico potential against SARS-CoV-2. Foods. 10, 1776 (2021).","DOI":"10.3390\/foods10081776"},{"key":"46778_CR12","doi-asserted-by":"crossref","unstructured":"Zheng, Y. et al. Oral propolis nanoemulsions modulate gut microbiota to balance bone remodeling for enhanced osteoporosis therapy. ACS Nano 18 (2024).","DOI":"10.1021\/acsnano.4c07332"},{"key":"46778_CR13","doi-asserted-by":"publisher","first-page":"46","DOI":"10.1186\/s13287-023-03273-z","volume":"14","author":"W Wan","year":"2023","unstructured":"Wan, W. et al. Human umbilical cord mesenchymal stem cells conditioned medium exerts anti-tumor effects on KGN cells in a cell density-dependent manner through activation of the Hippo pathway. Stem Cell. Res. Ther. 14, 46 (2023).","journal-title":"Stem Cell. Res. Ther."},{"key":"46778_CR14","doi-asserted-by":"publisher","first-page":"706","DOI":"10.1002\/jcp.29004","volume":"235","author":"H Abbaszadeh","year":"2020","unstructured":"Abbaszadeh, H. et al. Human umbilical cord mesenchymal stem cell-derived extracellular vesicles: A novel therapeutic paradigm. J. Cell. Physiol. 235, 706\u2013717 (2020).","journal-title":"J. Cell. Physiol."},{"key":"46778_CR15","doi-asserted-by":"publisher","unstructured":"Md Fadilah, N. I. et al. Cell secretomes for wound healing and tissue regeneration: Next generation acellular based tissue engineered products. J. Tissue Eng. 13 https:\/\/doi.org\/10.1177\/20417314221114273 (2022).","DOI":"10.1177\/20417314221114273"},{"key":"46778_CR16","doi-asserted-by":"publisher","first-page":"383","DOI":"10.1177\/0394632017740976","volume":"30","author":"TS Rajan","year":"2017","unstructured":"Rajan, T. S., Diomede, F., Bramanti, P., Trubiani, O. & Mazzon, E. Conditioned medium from human gingival mesenchymal stem cells protects motor-neuron-like NSC-34 cells against scratch-injury-induced cell death. Int. J. Immunopathol. Pharmacol. 30, 383\u2013394 (2017).","journal-title":"Int. J. Immunopathol. Pharmacol."},{"key":"46778_CR17","doi-asserted-by":"publisher","first-page":"101430","DOI":"10.1016\/j.jobcr.2026.101430","volume":"16","author":"PC Situmorang","year":"2026","unstructured":"Situmorang, P. C. et al. HUC-MSC secretome and nanoemulsion propolis synergistically modulate inflammatory responses in hyperglycemia-induced calvarial osteolysis. J. Oral Biol. Craniofac. Res. 16, 101430 (2026).","journal-title":"J. Oral Biol. Craniofac. Res."},{"key":"46778_CR18","doi-asserted-by":"publisher","first-page":"855","DOI":"10.1002\/jbmr.2103","volume":"29","author":"KM Sinha","year":"2014","unstructured":"Sinha, K. M., Yasuda, H., Zhou, X., de Crombrugghe, B. & Osterix NO66 histone demethylase control the chromatin architecture of Osterix target genes during osteoblast differentiation. J. Bone Min. Res. 29, 855\u2013865 (2014).","journal-title":"J. Bone Min. Res."},{"key":"46778_CR19","doi-asserted-by":"publisher","first-page":"27105","DOI":"10.1074\/jbc.M114.576793","volume":"289","author":"N Artigas","year":"2014","unstructured":"Artigas, N. et al. Mitogen-activated protein kinase (MAPK)-regulated interactions between osterix and RUNX2 are critical for the transcriptional osteogenic program. J. Biol. Chem. 289, 27105\u201327117 (2014).","journal-title":"J. Biol. Chem."},{"key":"46778_CR20","doi-asserted-by":"publisher","first-page":"86","DOI":"10.1038\/s41420-024-01856-0","volume":"10","author":"K Gan","year":"2024","unstructured":"Gan, K. et al. Periplogenin attenuates LPS-mediated inflammatory osteolysis through the suppression of osteoclastogenesis via reducing the NF-\u03baB and MAPK signaling pathways. Cell. Death Discov. 10, 86 (2024).","journal-title":"Cell. Death Discov"},{"key":"46778_CR21","doi-asserted-by":"publisher","first-page":"103","DOI":"10.1016\/j.jare.2024.05.004","volume":"70","author":"CM Trigo","year":"2025","unstructured":"Trigo, C. M. et al. Mesenchymal stem cell secretome for regenerative medicine: Where do we stand? J. Adv. Res. 70, 103\u2013124 (2025).","journal-title":"J. Adv. Res."},{"key":"46778_CR22","doi-asserted-by":"publisher","first-page":"1492","DOI":"10.7150\/ijms.87472","volume":"20","author":"L Li","year":"2023","unstructured":"Li, L. et al. Human umbilical cord mesenchymal stem cells in diabetes mellitus and its complications: applications and research advances. Int. J. Med. Sci. 20, 1492\u20131507 (2023).","journal-title":"Int. J. Med. Sci."},{"key":"46778_CR23","doi-asserted-by":"publisher","first-page":"e13586","DOI":"10.1111\/cpr.13586","volume":"57","author":"X Li","year":"2024","unstructured":"Li, X. et al. Umbilical cord-derived mesenchymal stem cell secretome promotes skin regeneration and rejuvenation: From mechanism to therapeutics. Cell. Prolif. 57, e13586 (2024).","journal-title":"Cell. Prolif."},{"key":"46778_CR24","doi-asserted-by":"publisher","first-page":"2307","DOI":"10.3390\/biomedicines10092307","volume":"10","author":"IN Amirrah","year":"2022","unstructured":"Amirrah, I. N. et al. A comprehensive review on collagen type i development of biomaterials for tissue engineering: from biosynthesis to bioscaffold. Biomedicines 10, 2307 (2022).","journal-title":"Biomedicines"},{"key":"46778_CR25","doi-asserted-by":"publisher","first-page":"101","DOI":"10.4103\/jofs.jofs_51_20","volume":"12","author":"TA Arianda","year":"2020","unstructured":"Arianda, T. A. et al. Effect of cocoa administration on osteoblast counts and alkaline phosphatase levels during orthodontic tooth movement in rats. J. Orofac. Sci. 12, 101\u2013106 (2020).","journal-title":"J. Orofac. Sci."},{"key":"46778_CR26","doi-asserted-by":"publisher","first-page":"194","DOI":"10.1016\/j.actbio.2020.04.040","volume":"120","author":"B Depalle","year":"2021","unstructured":"Depalle, B. et al. Osteopontin regulates type I collagen fibril formation in bone tissue. Acta Biomater. 120, 194\u2013202 (2021).","journal-title":"Acta Biomater."},{"key":"46778_CR27","doi-asserted-by":"publisher","first-page":"e919159","DOI":"10.12659\/MSM.919159","volume":"26","author":"J Si","year":"2020","unstructured":"Si, J. et al. Osteopontin in bone metabolism and bone diseases. Med. Sci. Monit. 26, e919159 (2020).","journal-title":"Med. Sci. Monit."},{"key":"46778_CR28","doi-asserted-by":"publisher","first-page":"435","DOI":"10.1007\/s00109-024-02418-8","volume":"102","author":"M Martiniakova","year":"2024","unstructured":"Martiniakova, M. et al. Current knowledge of bone-derived factor osteocalcin: its role in the management and treatment of diabetes mellitus, osteoporosis, osteopetrosis and inflammatory joint diseases. J. Mol. Med. 102, 435\u2013452 (2024).","journal-title":"J. Mol. Med."},{"key":"46778_CR29","doi-asserted-by":"publisher","first-page":"485","DOI":"10.1007\/s11914-023-00808-4","volume":"21","author":"H Hojo","year":"2023","unstructured":"Hojo, H. & Ohba, S. Runt-related transcription factors and gene regulatory mechanisms in skeletal development and diseases. Curr. Osteoporos. Rep. 21, 485\u2013492 (2023).","journal-title":"Curr. Osteoporos. Rep."},{"key":"46778_CR30","doi-asserted-by":"publisher","first-page":"169","DOI":"10.1186\/s13287-025-04288-4","volume":"16","author":"L Dalle Carbonare","year":"2025","unstructured":"Dalle Carbonare, L. et al. The bone microenvironment: new insights into the role of stem cells and cell communication in bone regeneration. Stem Cell. Res. Ther. 16, 169 (2025).","journal-title":"Stem Cell. Res. Ther."},{"key":"46778_CR31","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1038\/s44324-024-00010-9","volume":"2","author":"IA Choi","year":"2024","unstructured":"Choi, I. A. et al. Bone metabolism \u2013 an underappreciated player. npj Metab. Health Dis. 2, 12 (2024).","journal-title":"npj Metab. Health Dis."},{"key":"46778_CR32","doi-asserted-by":"publisher","first-page":"e2500885","DOI":"10.1002\/adhm.202500885","volume":"15","author":"S Raik","year":"2025","unstructured":"Raik, S. et al. Secretome derived from mesenchymal stem cells cultured as monolayer show enhanced bone regeneration compared to secretome from 3d spheroid - clues from the proteome. Adv. Health Mater. 15, e2500885 (2025).","journal-title":"Adv. Health Mater."},{"key":"46778_CR33","doi-asserted-by":"publisher","first-page":"2625","DOI":"10.1002\/jcp.31115","volume":"238","author":"RD Calixto","year":"2023","unstructured":"Calixto, R. D. et al. Effect of the secretome of mesenchymal stem cells overexpressing BMP-9 on osteoblast differentiation and bone repair. J. Cell. Physiol. 238, 2625\u20132637 (2023).","journal-title":"J. Cell. Physiol."},{"key":"46778_CR34","doi-asserted-by":"publisher","first-page":"134","DOI":"10.1186\/s13287-016-0392-2","volume":"7","author":"J Xu","year":"2016","unstructured":"Xu, J. et al. Human fetal mesenchymal stem cell secretome enhances bone consolidation in distraction osteogenesis. Stem Cell. Res. Ther. 7, 134 (2016).","journal-title":"Stem Cell. Res. Ther."},{"key":"46778_CR35","doi-asserted-by":"publisher","first-page":"3156","DOI":"10.3390\/molecules26113156","volume":"26","author":"SO Ekeuku","year":"2021","unstructured":"Ekeuku, S. O. & Chin, K. Y. Application of propolis in protecting skeletal and periodontal health-a systematic review. Molecules 26, 3156 (2021).","journal-title":"Molecules"},{"key":"46778_CR36","doi-asserted-by":"publisher","first-page":"81","DOI":"10.3390\/antiox14010081","volume":"14","author":"V Bertolucci","year":"2025","unstructured":"Bertolucci, V. et al. Bioactive compounds from propolis on bone homeostasis: a narrative review. Antioxid. (Basel). 14, 81\u201393 (2025).","journal-title":"Antioxid. (Basel)"},{"key":"46778_CR37","doi-asserted-by":"publisher","first-page":"11447","DOI":"10.1038\/s41598-019-47836-8","volume":"9","author":"TS Ayala","year":"2019","unstructured":"Ayala, T. S. et al. High glucose environments interfere with bone marrow-derived macrophage inflammatory mediator release, the TLR4 pathway and glucose metabolism. Sci. Rep. 9, 11447 (2019).","journal-title":"Sci. Rep."}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-026-46778-2","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-026-46778-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-026-46778-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T22:33:05Z","timestamp":1774996385000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-026-46778-2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,30]]},"references-count":37,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["46778"],"URL":"https:\/\/doi.org\/10.1038\/s41598-026-46778-2","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,30]]},"assertion":[{"value":"23 July 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"27 March 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"30 March 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"10612"}}