{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T02:45:52Z","timestamp":1782701152943,"version":"3.54.5"},"reference-count":48,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2026,6,28]],"date-time":"2026-06-28T00:00:00Z","timestamp":1782604800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Marine Drugs"],"abstract":"<jats:p>Osteosarcoma remains the most common primary malignant bone tumor in adolescents and is characterized by aggressive metastasis, resistance to therapy, and extensive bone microenvironment remodeling. Therefore, the identification of novel multi-target therapeutic agents capable of simultaneously inducing ferroptosis and disrupting tumor-supportive signaling is urgently needed. This study employed a multi-omics-guided approach to investigate the anti-osteosarcoma potential of metabolites derived from the sea cucumber Holothuria scabra. LC\u2013MS\/MS profiling identified major bioactive constituents, including holothurins, scabrasides, fucosterol, desmosterol, and 24-methylenecholesterol. Integrated transcriptomic analysis of the GSE42352 dataset revealed key ferroptosis- and bone microenvironment-associated targets, including CXCR4, CTSK, RUNX2, VEGFA, and TFRC. In silico pharmacological prediction and molecular docking demonstrated favorable anticancer properties and strong binding affinities of several metabolites toward these targets, with fucosterol and holothurin A exhibiting the most promising interactions. Functional validation in MG-63 osteosarcoma cells showed concentration-dependent reductions in cell viability and migration following H. scabra treatment. Furthermore, treatment decreased GPX4, NRF2, and GSH levels while increasing TFRC and MDA, indicating activation of ferroptotic cell death. In a MG-63\/RAW264.7 co-culture model, H. scabra suppressed RANKL, VEGFA, MMP9, and TRAP-positive osteoclast formation, suggesting inhibition of osteoclastogenesis, angiogenesis, and metastatic potential. Collectively, these findings identify H. scabra as a promising marine source of multi-target compounds for osteosarcoma management through coordinated induction of ferroptosis and remodeling of the bone tumor microenvironment.<\/jats:p>","DOI":"10.3390\/md24070226","type":"journal-article","created":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T02:16:44Z","timestamp":1782699404000},"page":"226","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Multi-Omics-Guided Discovery of Holothuria scabra-Derived Drug Candidates Targeting Ferroptosis and the Bone Tumor Microenvironment in Osteosarcoma"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6779-8921","authenticated-orcid":false,"given":"Jeremy Nicolas","family":"Sibarani","sequence":"first","affiliation":[{"name":"Faculty of Medicine, Universitas Airlangga, Surabaya 60132, Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammad Adib","family":"Khumaidi","sequence":"additional","affiliation":[{"name":"Faculty of Medicine and Health, Universitas Muhammadiyah Jakarta, Central Jakarta 10510, Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yudha Mathan","family":"Sakti","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics and Traumatology, Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada, Dr. Sardjito General Hospital, Yogyakarta 55281, Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4777-624X","authenticated-orcid":false,"given":"Happy Kurnia","family":"Permatasari","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Biomolecular, Faculty of Medicine, Universitas Brawijaya, Malang 65145, Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-9222-1173","authenticated-orcid":false,"given":"Adha Fauzi","family":"Hendrawan","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada, Yogyakarta 55281, Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8165-2072","authenticated-orcid":false,"given":"Reggie","family":"Surya","sequence":"additional","affiliation":[{"name":"Food Technology Department, Faculty of Engineering, Binus University, Jakarta 11480, Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-2759-4850","authenticated-orcid":false,"given":"Gioconda","family":"Millotti","sequence":"additional","affiliation":[{"name":"Faculty of Natural Sciences, Juraj Dobrila University of Pula, Zagreba\u010dka 30, 52100 Pula, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-0544-2807","authenticated-orcid":false,"given":"Edwin","family":"Hadinata","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Universitas Ciputra, Surabaya 60219, Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8929-1614","authenticated-orcid":false,"given":"Ines","family":"Kova\u010di\u0107","sequence":"additional","affiliation":[{"name":"Faculty of Natural Sciences, Juraj Dobrila University of Pula, Zagreba\u010dka 30, 52100 Pula, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raymond Rubianto","family":"Tjandrawinata","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, Faculty of Biotechnology, Atma Jaya Catholic University of Indonesia, Jakarta 12930, Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2151-0854","authenticated-orcid":false,"given":"Fahrul","family":"Nurkolis","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Universitas Airlangga, Surabaya 60132, Indonesia"},{"name":"Institute for Research and Community Service, State Islamic University of Sunan Kalijaga, Yogyakarta 55281, Indonesia"},{"name":"Medical Research Center of Indonesia, Surabaya 60281, Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1038\/s41572-022-00409-y","article-title":"Osteosarcoma","volume":"8","author":"Beird","year":"2022","journal-title":"Nat. Rev. Dis. Primers"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Lee, J.A., Lim, J., Jin, H.Y., Park, M., Park, H.J., Park, J.W., Kim, J.H., Kang, H.G., and Won, Y.-J. (2021). Osteosarcoma in Adolescents and Young Adults. Cells, 10.","DOI":"10.3390\/cells10102684"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"622","DOI":"10.1136\/archdischild-2024-327879","article-title":"Clinical Presentation of Bone Tumours in Children and Young People: A Systematic Review and Meta-Analysis","volume":"110","author":"Liu","year":"2025","journal-title":"Arch. Dis. Child."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Gazouli, I., Kyriazoglou, A., Kotsantis, I., Anastasiou, M., Pantazopoulos, A., Prevezanou, M., Chatzidakis, I., Kavourakis, G., Economopoulou, P., and Kontogeorgakos, V. (2021). Systematic Review of Recurrent Osteosarcoma Systemic Therapy. Cancers, 13.","DOI":"10.3390\/cancers13081757"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1038\/s41392-024-01885-2","article-title":"Mechanism Insights and Therapeutic Intervention of Tumor Metastasis: Latest Developments and Perspectives","volume":"9","author":"Shi","year":"2024","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Tarone, L., Iacoviello, A., Di Lorenzo, A., Verta, R., Cossu, C., Conti, L., Cavallo, F., and Riccardo, F. (2025). Exploring Emerging Therapeutic Targets in Osteosarcoma by Revisiting the Immune and Cancer-Intrinsic Hallmarks of Cancer. Cancers, 17.","DOI":"10.3390\/cancers17233846"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"101569","DOI":"10.1016\/j.gendis.2025.101569","article-title":"Tumor Microenvironment in Osteosarcoma: From Cellular Mechanism to Clinical Therapy","volume":"12","author":"Yu","year":"2025","journal-title":"Genes Dis."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"100729","DOI":"10.1016\/j.jbo.2025.100729","article-title":"The Regulatory Networks and Mechanisms of Bone Microenvironment in Tumorigenesis and Metastasis","volume":"55","author":"Huang","year":"2025","journal-title":"J. Bone Oncol."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Verrecchia, F., and R\u00e9dini, F. (2018). Transforming Growth Factor-\u03b2 Signaling Plays a Pivotal Role in the Interplay between Osteosarcoma Cells and Their Microenvironment. Front. Oncol., 8.","DOI":"10.3389\/fonc.2018.00133"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Ouyang, X., Ma, Q., Zhou, C., Tang, J., Li, M., Qing, J., Lei, X., Huang, D., Liu, H., and Zhang, G. (2025). Natural Bioactive Products in the Regulation of Bone Metabolism and Regeneration. Front. Pharmacol., 16.","DOI":"10.3389\/fphar.2025.1683279"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Veronesi, F., Tschon, M., and Fini, M. (2017). Gene Expression in Osteolysis: Review on the Identification of Altered Molecular Pathways in Preclinical and Clinical Studies. Int. J. Mol. Sci., 18.","DOI":"10.3390\/ijms18030499"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1439","DOI":"10.1007\/s00204-023-03476-6","article-title":"ROS-Induced Lipid Peroxidation Modulates Cell Death Outcome: Mechanisms behind Apoptosis, Autophagy, and Ferroptosis","volume":"97","author":"Wang","year":"2023","journal-title":"Arch. Toxicol."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Buglione, A., Gioia, M., Sinibaldi, F., Marini, S., and Ciaccio, C. (2025). Iron-Related Metabolic Targets in the Treatment of Osteosarcoma: Research Progress and Prospects. Biomedicines, 13.","DOI":"10.20944\/preprints202509.1346.v1"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"103498","DOI":"10.1016\/j.tice.2026.103498","article-title":"Mitophagy at the Intersection of Ferroptosis and Cuproptosis in Osteosarcoma: Molecular Interactions and Therapeutic Implications","volume":"101","author":"Fang","year":"2026","journal-title":"Tissue Cell"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1186\/s43556-023-00142-2","article-title":"The Mechanism of Ferroptosis and Its Related Diseases","volume":"4","author":"Feng","year":"2023","journal-title":"Mol. Biomed."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Ibrahim, H.A.H., and El-Sheekh, M.M. (2023). Marine Ecosystems: A Unique Source of Valuable Bioactive Compounds, Bentham Science.","DOI":"10.2174\/97898150519951230301"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"107868","DOI":"10.1016\/j.phrs.2025.107868","article-title":"Marine Bioactives: Pioneering Sustainable Solutions for Advanced Cosmetics and Therapeutics","volume":"218","author":"Nurkolis","year":"2025","journal-title":"Pharmacol. Res."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Salindeho, N., Nurkolis, F., Gunawan, W.B., Handoko, M.N., Samtiya, M., and Muliadi, R.D. (2022). Anticancer and Anticholesterol Attributes of Sea Cucumbers: An Opinion in Terms of Functional Food Applications. Front. Nutr., 9.","DOI":"10.3389\/fnut.2022.986986"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Brown, K.T., Southgate, P.C., Duy, N.D.Q., Havimana, L., Mmochi, A.J., Basiita, R.K., Delghandi, M., Stockwell, B., and Lal, M.M. (2025). The Sandfish Identity: Phylogeographic Reconstructions Uncover a Species Complex within the Indo-Pacific Distribution of Holothuria (Metriatyla) Scabra. BMC Ecol. Evol., 25.","DOI":"10.1186\/s12862-025-02421-8"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1315","DOI":"10.1007\/s11101-021-09783-z","article-title":"Holothuria Triterpene Glycosides: A Comprehensive Guide for Their Structure Elucidation and Critical Appraisal of Reported Compounds","volume":"21","author":"Puspitasari","year":"2022","journal-title":"Phytochem. Rev."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Hossain, A., Dave, D., and Shahidi, F. (2022). Antioxidant Potential of Sea Cucumbers and Their Beneficial Effects on Human Health. Mar. Drugs, 20.","DOI":"10.3390\/md20080521"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Menchinskaya, E.S., Chingizova, E.A., Pislyagin, E.A., Yurchenko, E.A., Klimovich, A.A., Zelepuga, E.A., Aminin, D.L., Avilov, S.A., and Silchenko, A.S. (2024). Mechanisms of Action of Sea Cucumber Triterpene Glycosides Cucumarioside A0-1 and Djakonovioside A against Human Triple-Negative Breast Cancer. Mar. Drugs, 22.","DOI":"10.3390\/md22100474"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"310","DOI":"10.3390\/md23080310","article-title":"Therapeutic Potential of Sea Cucumber-Derived Bioactives in the Prevention and Management of Brain-Related Disorders: A Comprehensive Review","volume":"23","author":"Debi","year":"2025","journal-title":"Mar. Drugs"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"112847","DOI":"10.4239\/wjd.v16.i11.112847","article-title":"Mechanisms behind the Anti-Diabetic and Anti-Obesity Effects of Seaweeds or Macroalgae and Their Bioactive Compounds","volume":"16","author":"Magwaza","year":"2025","journal-title":"World J. Diabetes"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"118023","DOI":"10.1016\/j.biopha.2025.118023","article-title":"Targeting VEGF Signaling for Tumor Microenvironment Remodeling and Metastasis Inhibition: Therapeutic Strategies and Insights","volume":"186","author":"Mahaki","year":"2025","journal-title":"Biomed. Pharmacother."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"2412","DOI":"10.1111\/cas.13653","article-title":"CXCR4-Mediated Osteosarcoma Growth and Pulmonary Metastasis Is Suppressed by MicroRNA-613","volume":"109","author":"Zhu","year":"2018","journal-title":"Cancer Sci."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Nirala, B.K., Yamamichi, T., and Yustein, J.T. (2023). Deciphering the Signaling Mechanisms of Osteosarcoma Tumorigenesis. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms241411367"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Correnti, M., Gammella, E., Cairo, G., and Recalcati, S. (2026). The Interplay between Bone Biology and Iron Metabolism: Molecular Mechanisms and Clinical Implications. Biomedicines, 14.","DOI":"10.3390\/biomedicines14020301"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1964","DOI":"10.1080\/01635581.2020.1814825","article-title":"Holothuria scabra Extract Induces Cell Apoptosis and Suppresses Warburg Effect by Down-Regulating Akt\/mTOR\/HIF-1 Axis in MDA-MB-231 Breast Cancer Cells","volume":"73","author":"Yurasakpong","year":"2021","journal-title":"Nutr. Cancer"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"820","DOI":"10.1007\/s10637-017-0505-5","article-title":"Mechanisms of Cancer Cell Killing by Sea Cucumber-Derived Compounds","volume":"35","author":"Wargasetia","year":"2017","journal-title":"Investig. New Drugs"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Sheng, G., Gao, Y., Yang, Y., and Wu, H. (2021). Osteosarcoma and Metastasis. Front. Oncol., 11.","DOI":"10.3389\/fonc.2021.780264"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Singh, M., Arora, H.L., Naik, R., Joshi, S., Sonawane, K., Sharma, N.K., and Sinha, B.K. (2025). Ferroptosis in Cancer: Mechanism and Therapeutic Potential. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26083852"},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Voros, C., Chatzinikolaou, F., Papadimas, G., Polykalas, S., Mavrogianni, D., Koulakmanidis, A.-M., Athanasiou, D., Kanaka, V., Bananis, K., and Athanasiou, A. (2026). Oxidative Stress and SIRT1-Nrf2 Anti-Ferroptotic Pathways in Granulosa Cells: A Molecular Key to Follicular Atresia and Ovarian Aging. Int. J. Mol. Sci., 27.","DOI":"10.3390\/ijms27020950"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Elaasser, B., Arakil, N., and Mohammad, K.S. (2024). Bridging the Gap in Understanding Bone Metastasis: A Multifaceted Perspective. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25052846"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"919","DOI":"10.56499\/jppres24.2069_13.3.919","article-title":"Extract of Holothuria scabra Exhibits Synergistic Effect with Chemotherapeutic Agents against Breast Cancer in Vitro","volume":"13","author":"Wargasetia","year":"2025","journal-title":"J. Pharm. Pharmacogn. Res."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Nurkolis, F., d\u2019Arqom, A., Apryani, E., Fatimah, N., Hendrawan, A.F., Afkarina, I., Surya, R., Permatasari, H.K., Harbuwono, D.S., and Taslim, N.A. (2026). Integrative Metabolomics and Systems Pharmacology Reveal PPAR\u03b3-Centered Antidiabetic Mechanisms of Caulerpa Racemosa and Its Bioactive Compounds. Mar. Drugs, 24.","DOI":"10.3390\/md24020082"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1007\/s00217-025-04928-2","article-title":"Metabolomics, Chemometrics, in Silico and in Vitro Analyses Reveal Functional Food Phytochemicals of Indonesian Spices for Antioxidant, Anticancer, Anti-Aging, and Anti-Obesity Potential","volume":"252","author":"Tjandrawinata","year":"2026","journal-title":"Eur. Food Res. Technol."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Ikrar, T., Siahaan, S.C., Hendarto, H., Mustika, A., Kurniawati, E.M., Jatipradresthya, W., Hadinata, E., Taslim, N.A., Harbuwono, D.S., and Tjandrawinata, R.R. (2026). Multi-Target Modulation of Metabolic and Steroidogenic Pathways by Cinnamomum Burmannii and Myristica Fragrans in Polycystic Ovary Syndrome: An Integrative Transcriptomics, Metabolomic, Pharmacoinformatics and Experimental Validation. Nutrients, 18.","DOI":"10.3390\/nu18081305"},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Kuijjer, M.L., Peterse, E.F.P., van den Akker, B.E.W.M., Briaire-de Bruijn, I.H., Serra, M., Meza-Zepeda, L.A., Myklebost, O., Hassan, A.B., Hogendoorn, P.C.W., and Cleton-Jansen, A.-M. (2013). IR\/IGF1R Signaling as Potential Target for Treatment of High-Grade Osteosarcoma. BMC Cancer, 13.","DOI":"10.1186\/1471-2407-13-245"},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Kuijjer, M.L., van den Akker, B.E.W.M., Hilhorst, R., Mommersteeg, M., Buddingh, E.P., Serra, M., B\u00fcrger, H., Hogendoorn, P.C.W., and Cleton-Jansen, A.-M. (2014). Kinome and mRNA Expression Profiling of High-Grade Osteosarcoma Cell Lines Implies Akt Signaling as Possible Target for Therapy. BMC Med. Genom., 7.","DOI":"10.1186\/1755-8794-7-4"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"D1516","DOI":"10.1093\/nar\/gkae1059","article-title":"PubChem 2025 Update","volume":"53","author":"Kim","year":"2025","journal-title":"Nucleic Acids Res."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"D587","DOI":"10.1093\/nar\/gkac963","article-title":"KEGG for Taxonomy-Based Analysis of Pathways and Genomes","volume":"51","author":"Kanehisa","year":"2023","journal-title":"Nucleic Acids Res."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Liu, Y., Ding, J., Gan, J., Xiong, X., Zong, F., Xiao, Z.-X., and Cao, Y. (2026). CB-Dock3: An Enhanced Web Server for Protein-Ligand Blind Docking. Nucleic Acids Res., gkag417.","DOI":"10.1093\/nar\/gkag417"},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Yun, H.-M., Kim, S.H., Kwon, Y.-J., and Park, K.-R. (2024). Effect of Spicatoside a on Anti-Osteosarcoma MG63 Cells through Reactive Oxygen Species Generation and the Inhibition of the PI3K-AKT-mTOR Pathway. Antioxidants, 13.","DOI":"10.3390\/antiox13101162"},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Karabat, M.U., and Tuncer, M.C. (2025). PI3K\/Akt1 Pathway Suppression by Quercetin-Doxorubicin Combination in Osteosarcoma Cell Line (MG-63 Cells). Medicina, 61.","DOI":"10.3390\/medicina61081347"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"101988","DOI":"10.1016\/j.mcp.2024.101988","article-title":"Honokiol Inhibits Human Osteosarcoma MG63 Cell Migration by Upregulating FTO and Smad6 to Promote Autophagy","volume":"78","author":"Wu","year":"2024","journal-title":"Mol. Cell. Probes"},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Cheng, Y., Liu, H., Li, J., Ma, Y., Song, C., Wang, Y., Li, P., Chen, Y., and Zhang, Z. (2022). Evaluation of Culture Conditions for Osteoclastogenesis in RAW264.7 Cells. PLoS ONE, 17.","DOI":"10.1371\/journal.pone.0277871"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"22741","DOI":"10.1038\/s41598-021-02139-9","article-title":"Nanovibrational Stimulation Inhibits Osteoclastogenesis and Enhances Osteogenesis in Co-Cultures","volume":"11","author":"Kennedy","year":"2021","journal-title":"Sci. Rep."}],"container-title":["Marine Drugs"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1660-3397\/24\/7\/226\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T02:20:02Z","timestamp":1782699602000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1660-3397\/24\/7\/226"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,28]]},"references-count":48,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2026,7]]}},"alternative-id":["md24070226"],"URL":"https:\/\/doi.org\/10.3390\/md24070226","relation":{},"ISSN":["1660-3397"],"issn-type":[{"value":"1660-3397","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,28]]}}}