{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,11]],"date-time":"2026-03-11T01:39:15Z","timestamp":1773193155745,"version":"3.50.1"},"reference-count":45,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2026,3,7]],"date-time":"2026-03-07T00:00:00Z","timestamp":1772841600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002467","name":"Dankook University","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100002467","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Magnolia kobus (M. kobus) has long been used to treat nasal congestion, allergic rhinitis, and sinusitis. In the current study, we demonstrate the effects and underlying mechanisms of M. kobus flower water extract (ME) and ME-derived constituent magnolin on in vitro osteoblastogenic and anti-osteoclastogenic responses. Treatment with ME or magnolin markedly enhanced the osteoblast differentiation and mineralization in MC3T3-E1 pre-osteoblasts. This osteoblastogenic activity of ME or magnolin was closely associated with upregulation of osteoblast-specific molecules, including RUNX2, DLX5, OSX, alkaline phosphatase, collagen type I, and osteopontin, as well as the activation of mitogen-activated protein kinase (MAPK) signaling pathways. Concurrently, magnolin inhibited osteoclast differentiation through inactivating MAPK pathways and downregulating NFATc1, c-Fos, tartrate-resistant acid phosphatase, and cathepsin K in RANKL-treated RAW264.7 cells. These observations suggest that ME and magnolin have pharmacological potential for the treatment and prevention of metabolic bone disorders, including osteoporosis.<\/jats:p>","DOI":"10.3390\/ijms27052472","type":"journal-article","created":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T10:16:12Z","timestamp":1773051372000},"page":"2472","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Novel Osteoblastogenic Activity of Magnolia kobus: The Pharmacological Potential for Osteoporosis"],"prefix":"10.3390","volume":"27","author":[{"given":"Do Hun","family":"Lee","sequence":"first","affiliation":[{"name":"College of Pharmacy, Dankook University, 119 Dandae-ro, Cheonan 31116, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ju-Hyoung","family":"Park","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Dankook University, 119 Dandae-ro, Cheonan 31116, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dong-Wan","family":"Seo","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Dankook University, 119 Dandae-ro, Cheonan 31116, Republic of Korea"},{"name":"Center for Human Risk Assessment, Dankook University, 119 Dandae-ro, Cheonan 31116, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1038\/s41421-024-00689-6","article-title":"Cell signaling and transcriptional regulation of osteoblast lineage commitment, differentiation, bone formation, and homeostasis","volume":"10","author":"Zhu","year":"2024","journal-title":"Cell Discov."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Gao, Y., Patil, S., and Jia, J. (2021). The development of molecular biology of osteoporosis. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22158182"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1","DOI":"10.22203\/eCM.v024a01","article-title":"In search of an osteoblast cell model for in vitro research","volume":"24","author":"Czekanska","year":"2012","journal-title":"Eur. Cells Mater."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Nagashima, D., Ishibashi, Y., Kawaguchi, S., Furukawa, M., Toho, M., Ohno, M., Nitto, T., and Izumo, N. (2022). Human recombinant lactoferrin promotes differentiation and calcification on MC3T3-E1 cells. Pharmaceutics, 15.","DOI":"10.3390\/pharmaceutics15010060"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Choi, H.K., Kim, G.J., Yoo, H.S., Song, D.H., Chung, K.H., Lee, K.J., Koo, Y.T., and An, J.H. (2019). Vitamin C activates osteoblastogenesis and inhibits osteoclastogenesis via Wnt\/\u03b2-catenin\/ATF4 signaling pathways. Nutrients, 11.","DOI":"10.3390\/nu11030506"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1186\/scrt328","article-title":"Effects of dexamethasone, ascorbic acid and \u03b2-glycerophosphate on the osteogenic differentiation of stem cells in vitro","volume":"4","author":"Langenbach","year":"2013","journal-title":"Stem Cell Res. Ther."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1038\/nrm3254","article-title":"Building strong bones: Molecular regulation of the osteoblast lineage","volume":"13","author":"Long","year":"2011","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Suzuki, R., Shirataki, Y., Tomomura, A., Bandow, K., Sakagami, H., and Tomomura, M. (2023). Isolation of pro-osteogenic compounds from Euptelea polyandra that reciprocally regulate osteoblast and osteoclast differentiation. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms242417479"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Amarasekara, D.S., Kim, S., and Rho, J. (2021). Regulation of osteoblast differentiation by cytokine networks. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22062851"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1233","DOI":"10.1002\/jcb.20958","article-title":"Regulation of osteoblast differentiation by transcription factors","volume":"99","author":"Komori","year":"2006","journal-title":"J. Cell. Biochem."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"11969","DOI":"10.1002\/jcp.27852","article-title":"Evaluation of efficacy on RANKL induced osteoclast from RAW264.7 cells","volume":"234","author":"Song","year":"2019","journal-title":"J. Cell. Physiol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1007\/s00774-020-01191-1","article-title":"RANKL as the master regulator of osteoclast differentiation","volume":"39","author":"Takayanagi","year":"2021","journal-title":"J. Bone Miner. Metab."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1016\/j.intimp.2016.04.024","article-title":"Natural products for treatment of bone erosive diseases: The effects and mechanisms on inhibiting osteoclastogenesis and bone resorption","volume":"36","author":"An","year":"2016","journal-title":"Int. Immunopharmacol."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Zhou, C., Shen, S., Zhang, M., Luo, H., Zhang, Y., Wu, C., Zeng, L., and Ruan, H. (2023). Mechanisms of action and synergetic formulas of plant-based natural compounds from traditional Chinese medicine for managing osteoporosis: A literature review. Front. Med., 10.","DOI":"10.3389\/fmed.2023.1235081"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"115271","DOI":"10.1016\/j.taap.2020.115271","article-title":"Targeting autophagy by natural product ursolic acid for prevention and treatment of osteoporosis","volume":"409","author":"Zheng","year":"2020","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"106635","DOI":"10.1016\/j.phrs.2022.106635","article-title":"Cell death regulation: A new way for natural products to treat osteoporosis","volume":"187","author":"Li","year":"2023","journal-title":"Pharmacol. Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"538","DOI":"10.3390\/cimb45010036","article-title":"Magnolia kobus extract inhibits periodontitis-inducing mediators in Porphyromonas gingivalis lipopolysaccharide-activated RAW 264.7 cells","volume":"45","author":"Lee","year":"2023","journal-title":"Curr. Issues Mol. Biol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1616","DOI":"10.2174\/092986708784911515","article-title":"Chemistry and bioactivity of Flos Magnoliae, a Chinese herb for rhinitis and sinusitis","volume":"15","author":"Shen","year":"2008","journal-title":"Curr. Med. Chem."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Bhuia, M.S., Wilairatana, P., Chowdhury, R., Rakib, A.I., Kamli, H., Shaikh, A., Coutinho, H.D.M., and Islam, M.T. (2023). Anticancer potentials of the lignan magnolin: A systematic review. Molecules, 28.","DOI":"10.3390\/molecules28093671"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"100203","DOI":"10.1016\/j.prmcm.2022.100203","article-title":"Therapeutic effectiveness of magnolin on cancers and other human complications","volume":"6","author":"Patel","year":"2023","journal-title":"Pharmacol. Res.\u2014Mod. Chin. Med."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"4875","DOI":"10.3390\/cimb45060310","article-title":"Magnolia kobus extract suppresses Porphyromonas gingivalis LPS-induced proinflammatory cytokine and MMP expression in HGF-1 cells and regulates osteoclastogenesis in RANKL-stimulated RAW264.7 cells","volume":"45","author":"Lee","year":"2023","journal-title":"Curr. Issues Mol. Biol."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Lee, C.J., Lee, M.H., Yoo, S.M., Choi, K.I., Song, J.H., Jang, J.H., Oh, S.R., Ryu, H.W., Lee, H.S., and Surh, Y.J. (2015). Magnolin inhibits cell migration and invasion by targeting the ERKs\/RSK2 signaling pathway. BMC Cancer, 15.","DOI":"10.1186\/s12885-015-1580-7"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1080\/03008207.2020.1778679","article-title":"Magnolin exhibits anti-inflammatory effects on chondrocytes via the NF-\u03baB pathway for attenuating anterior cruciate ligament transection-induced osteoarthritis","volume":"62","author":"Xu","year":"2021","journal-title":"Connect. Tissue Res."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"144855","DOI":"10.1016\/j.gene.2020.144855","article-title":"Alkaline phosphatase: Structure, expression and its function in bone mineralization","volume":"754","author":"Vimalraj","year":"2020","journal-title":"Gene"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"a031229","DOI":"10.1101\/cshperspect.a031229","article-title":"Mechanism of bone mineralization","volume":"8","author":"Murshed","year":"2018","journal-title":"Cold Spring Harb. Perspect. Med."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/j.ab.2004.02.002","article-title":"An alizarin red-based assay of mineralization by adherent cells in culture: Comparison with cetylpyridinium chloride extraction","volume":"329","author":"Gregory","year":"2004","journal-title":"Anal. Biochem."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Bernar, A., Gebetsberger, J.V., Bauer, M., Streif, W., and Schirmer, M. (2022). Optimization of the alizarin red S assay by enhancing mineralization of osteoblasts. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24010723"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Komori, T. (2020). Functions of osteocalcin in bone, pancreas, testis, and muscle. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21207513"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1","DOI":"10.11005\/jbm.2022.29.1.1","article-title":"The extracellular signal-regulated kinase mitogen-activated protein kinase pathway in osteoblasts","volume":"29","author":"Greenblatt","year":"2022","journal-title":"J. Bone Metab."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Rodr\u00edguez-Carballo, E., G\u00e1mez, B., and Ventura, F. (2016). p38 MAPK signaling in osteoblast differentiation. Front. Cell Dev. Biol., 4.","DOI":"10.3389\/fcell.2016.00040"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1152\/physiol.00061.2014","article-title":"Physiological bone remodeling: Systemic regulation and growth factor involvement","volume":"31","author":"Siddiqui","year":"2016","journal-title":"Physiology"},{"key":"ref_32","first-page":"421746","article-title":"Biology of bone tissue: Structure, function, and factors that influence bone cells","volume":"2015","author":"Sasso","year":"2015","journal-title":"Biomed Res. Int."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"15005","DOI":"10.1038\/boneres.2015.5","article-title":"TGF-\u03b2\/BMP signaling and other molecular events: Regulation of osteoblastogenesis and bone formation","volume":"3","author":"Rahman","year":"2015","journal-title":"Bone Res."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1146\/annurev.cellbio.042308.113308","article-title":"Genetic control of bone formation","volume":"25","author":"Karsenty","year":"2009","journal-title":"Annu. Rev. Cell Dev. Biol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1083\/jcb.200610046","article-title":"Critical role of the extracellular signal-regulated kinase-MAPK pathway in osteoblast differentiation and skeletal development","volume":"176","author":"Ge","year":"2007","journal-title":"J. Cell Biol."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Chan, W.C.W., Tan, Z., To, M.K.T., and Chan, D. (2021). Regulation and role of transcription factors in osteogenesis. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22115445"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1006\/bbrc.1999.1639","article-title":"Serial passage of MC3T3-E1 cells alters osteoblastic function and responsiveness to transforming growth factor-\u03b21 and bone morphogenetic protein-2","volume":"265","author":"Chung","year":"1999","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Lee, J.A., Shin, J.Y., Hong, S.S., Cho, Y.R., Park, J.H., Seo, D.W., Oh, J.S., Kang, J.S., Lee, J.H., and Ahn, E.K. (2022). Tetracera loureiri extract regulates lipopolysaccharide-induced inflammatory response via nuclear factor-\u03baB and mitogen activated protein kinase signaling pathways. Plants, 11.","DOI":"10.3390\/plants11030284"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1016\/S0092-8674(03)00551-8","article-title":"TIMP-2 mediated inhibition of angiogenesis: An MMP-independent mechanism","volume":"114","author":"Seo","year":"2003","journal-title":"Cell"},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Park, S.H., An, H.J., Kim, H., Song, I., and Lee, S. (2024). Contribution of osteoblast and osteoclast supernatants to bone formation: Determination using a novel microfluidic chip. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25126605"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1038\/s41420-022-00904-x","article-title":"Osteopontin aggravates acute lung injury in influenza virus infection by promoting macrophages necroptosis","volume":"8","author":"Wang","year":"2022","journal-title":"Cell Death Discov."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1016\/j.bbrc.2017.02.062","article-title":"Staphylococcal lipoteichoic acid promotes osteogenic differentiation of mouse mesenchymal stem cells by increasing autophagic activity","volume":"485","author":"Liu","year":"2017","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"115","DOI":"10.14715\/cmb\/2024.70.11.17","article-title":"Reduction in integrin \u03b13\u03b21 modulates lung cancer motility and invasion through p70S6K-dependent E-cadherin localization","volume":"70","author":"Cho","year":"2024","journal-title":"Cell. Mol. Biol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"101546","DOI":"10.1016\/j.tranon.2022.101546","article-title":"A novel telomerase-derived peptide GV1001-mediated inhibition of angiogenesis: Regulation of VEGF\/VEGFR-2 signaling pathways","volume":"26","author":"Kim","year":"2022","journal-title":"Transl. Oncol."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Shuang, Y., Yizhen, L., Zhang, Y., Fujioka-Kobayashi, M., Sculean, A., and Miron, R.J. (2016). In vitro characterization of an osteoinductive biphasic calcium phosphate in combination with recombinant BMP2. BMC Oral Health, 17.","DOI":"10.1186\/s12903-016-0263-3"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/5\/2472\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,10]],"date-time":"2026-03-10T05:18:37Z","timestamp":1773119917000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/5\/2472"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,7]]},"references-count":45,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2026,3]]}},"alternative-id":["ijms27052472"],"URL":"https:\/\/doi.org\/10.3390\/ijms27052472","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,7]]}}}