{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,8]],"date-time":"2026-01-08T12:01:40Z","timestamp":1767873700741,"version":"3.49.0"},"reference-count":64,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2026,1,8]],"date-time":"2026-01-08T00:00:00Z","timestamp":1767830400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Research Foundation of Korea (NRF) grant funded by the Korea Government","award":["IRIS RS-2025-00518386"],"award-info":[{"award-number":["IRIS RS-2025-00518386"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Calcific aortic valve stenosis (CAVS) is a progressive cardiovascular disease associated with oxidative stress-driven osteogenic differentiation of valvular interstitial cells (VICs), yet no pharmacological therapy can prevent its progression. \u03b3-oryzanol (\u03b3-ORZ), a rice bran-derived phytosteryl ferulate, exhibits potent antioxidative and anti-inflammatory activities that may counteract valvular calcification. Here, we show that \u03b3-ORZ markedly attenuates PCM-induced intracellular ROS elevation, osteogenic differentiation, and calcium phosphate deposition in porcine VICs (pVICs). In addition, RT-qPCR and Western blot analyses revealed significant downregulation of calcification markers (RUNX2, OPN, BMP2), along with suppressed SMAD1\/5\/9 transcription and phosphorylation, decreased p38\/ERK MAPK activation, and reduced ALP activity. Collectively, these findings indicate that \u03b3-ORZ mitigates oxidative stress-mediated valvular calcification by inhibiting both canonical and non-canonical BMP2-SMAD\/MAPK signaling, suggesting its potential as a medicinal candidate for early intervention in CAVS.<\/jats:p>","DOI":"10.3390\/biom16010107","type":"journal-article","created":{"date-parts":[[2026,1,8]],"date-time":"2026-01-08T09:01:29Z","timestamp":1767862889000},"page":"107","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Gamma-Oryzanol Attenuates Aortic Valve Interstitial Cell Calcification via Suppression of BMP2-SMAD and MAPK Signaling Pathways"],"prefix":"10.3390","volume":"16","author":[{"given":"Mausam","family":"Thapa","sequence":"first","affiliation":[{"name":"College of Pharmacy, Mokpo National University, Muan 58554, Republic of Korea"},{"name":"Convergence Center for Green Anti-Aging Research, Mokpo National University, Muan 58554, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Saugat","family":"Shiwakoti","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Mokpo National University, Muan 58554, Republic of Korea"},{"name":"Convergence Center for Green Anti-Aging Research, Mokpo National University, Muan 58554, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dalseong","family":"Gong","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Mokpo National University, Muan 58554, Republic of Korea"},{"name":"Convergence Center for Green Anti-Aging Research, Mokpo National University, Muan 58554, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ju-Young","family":"Ko","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Mokpo National University, Muan 58554, Republic of Korea"},{"name":"Convergence Center for Green Anti-Aging Research, Mokpo National University, Muan 58554, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yeon-Hyang","family":"Gwak","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Mokpo National University, Muan 58554, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5584-1702","authenticated-orcid":false,"given":"Min-Ho","family":"Oak","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Mokpo National University, Muan 58554, Republic of Korea"},{"name":"Convergence Center for Green Anti-Aging Research, Mokpo National University, Muan 58554, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1055\/s-0042-1758382","article-title":"Calcific Aortic Valve Stenosis with Aging and Current Development in Its Pathophysiology","volume":"31","author":"Kodra","year":"2022","journal-title":"Int. J. Angiol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"724","DOI":"10.1016\/j.jacbts.2025.01.018","article-title":"Transcriptomic Signatures of Calcific Aortic Valve Stenosis Severity in Human Tricuspid and Bicuspid Aortic Valves","volume":"10","author":"Ursula","year":"2025","journal-title":"JACC Basic Transl. Sci."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Vassiliou, V.S., Johnson, N., Langlands, K., and Tsampasian, V. (2024). Genetics of Calcific Aortic Stenosis: A Systematic Review. Genes, 15.","DOI":"10.3390\/genes15101309"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"107318","DOI":"10.1016\/j.carpath.2021.107318","article-title":"Cellular senescence evaluated by P16INK4a immunohistochemistry is a prevalent phenomenon in advanced calcific aortic valve disease","volume":"52","author":"Christopher","year":"2021","journal-title":"Cardiovasc. Pathol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"e002244","DOI":"10.1136\/openhrt-2022-002244","article-title":"Pathophysiology, emerging techniques for the assessment and novel treatment of aortic stenosis","volume":"10","author":"Shah","year":"2023","journal-title":"Open Heart"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"2014","DOI":"10.1001\/jama.2024.16477","article-title":"Calcific Aortic Stenosis: A Review","volume":"332","author":"Otto","year":"2024","journal-title":"JAMA"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Donato, M., Ferri, N., Lupo, M.G., Faggin, E., and Rattazzi, M. (2020). Current Evidence and Future Perspectives on Pharmacological Treatment of Calcific Aortic Valve Stenosis. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21218263"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Juarez-Casso, F.M., and Crestanello, J.A. (2023). The Evolving Role of Surgical Aortic Valve Replacement in the Era of Transcatheter Valvular Procedures. J. Clin. Med., 12.","DOI":"10.3390\/jcm12165299"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"2618","DOI":"10.1093\/eurheartj\/ehx653","article-title":"Calcific aortic valve stenosis: Hard disease in the heart: A biomolecular approach towards diagnosis and treatment","volume":"39","author":"Peeters","year":"2017","journal-title":"Eur. Heart J."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Fan, P., Liu, Y., Qian, X., Tong, F., Zheng, Y., Fan, Z., Chen, M., Chen, Z., Zhai, H., and Zeng, T. (2025). Deciphering the Enigma of Calcific Aortic Valve Disease: The Pivotal Role of Animal Models in Unraveling Pathogenesis and Advancing Therapeutic Strategies. Biomedicines, 13.","DOI":"10.3390\/biomedicines13102369"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1433","DOI":"10.1093\/cvr\/cvab142","article-title":"Role of oxidative stress in calcific aortic valve disease and its therapeutic implications","volume":"118","author":"Greenberg","year":"2022","journal-title":"Cardiovasc. Res."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1161\/CIRCRESAHA.111.300084","article-title":"Current Management of Calcific Aortic Stenosis","volume":"113","author":"Brian","year":"2013","journal-title":"Circ. Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"e042112","DOI":"10.1161\/JAHA.125.042112","article-title":"Rationale and Design of the EPISODE Trial: A Randomized Controlled Trial on the Effect of PCSK9 Inhibitors in Calcific Aortic Valve Stenosis","volume":"14","author":"Yang","year":"2025","journal-title":"J. Am. Heart Assoc."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"e016911","DOI":"10.1161\/JAHA.120.016911","article-title":"Renin-Angiotensin System Blockade in Aortic Stenosis: Implications Before and After Aortic Valve Replacement","volume":"9","author":"Sachin","year":"2020","journal-title":"J. Am. Heart Assoc."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1641","DOI":"10.1093\/cvr\/cvad062","article-title":"Lipoprotein(a) and calcific aortic valve disease initiation and progression: A systematic review and meta-analysis","volume":"119","author":"Pantelidis","year":"2023","journal-title":"Cardiovasc. Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"109985","DOI":"10.1016\/j.biopha.2020.109985","article-title":"The natural compound andrographolide inhibits human aortic valve interstitial cell calcification via the NF-kappa B\/Akt\/ERK pathway","volume":"125","author":"Huang","year":"2020","journal-title":"Biomed. Pharmacother."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1038\/s41420-019-0225-z","article-title":"Natural and non-natural antioxidative compounds: Potential candidates for treatment of vascular calcification","volume":"5","author":"Chao","year":"2019","journal-title":"Cell Death Discov."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Liang, Y., Chen, G., Zhang, F., Yang, X., Chen, Y., Duan, Y., Yu, M., Zhang, S., and Han, J. (2021). Procyanidin B2 Reduces Vascular Calcification Through Inactivation of ERK1\/2-RUNX2 Pathway. Antioxidants, 10.","DOI":"10.3390\/antiox10060916"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/j.vph.2014.08.005","article-title":"Gallic acid inhibits vascular calcification through the blockade of BMP2\u2013Smad1\/5\/8 signaling pathway","volume":"63","author":"Kee","year":"2014","journal-title":"Vasc. Pharmacol."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Son, J.E., Jo, J.-Y., Kim, S., Park, M.J., Lee, Y., Park, S.S., Park, S.Y., Jung, S.M., Jung, S.K., and Kim, J.Y. (2023). Rice Bran Extract Suppresses High-Fat Diet-Induced Hyperlipidemia and Hepatosteatosis through Targeting AMPK and STAT3 Signaling. Nutrients, 15.","DOI":"10.3390\/nu15163630"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Mastinu, A., Bonini, S.A., Rungratanawanich, W., Aria, F., Marziano, M., Maccarinelli, G., Abate, G., Premoli, M., Memo, M., and Uberti, D. (2019). Gamma-Oryzanol Prevents LPS-induced Brain Inflammation and Cognitive Impairment in Adult Mice. Nutrients, 11.","DOI":"10.3390\/nu11040728"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"e20062","DOI":"10.7717\/peerj.20062","article-title":"Effectiveness of gamma-oryzanol in glycaemic control and managing oxidative stress, inflammation, and dyslipidaemia in diabetes: A systematic review of preclinical studies","volume":"13","author":"Radda","year":"2025","journal-title":"PeerJ"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Rungratanawanich, W., Cenini, G., Mastinu, A., Sylvester, M., Wilkening, A., Abate, G., Bonini, S.A., Aria, F., Marziano, M., and Maccarinelli, G. (2019). \u03b3-Oryzanol Improves Cognitive Function and Modulates Hippocampal Proteome in Mice. Nutrients, 11.","DOI":"10.3390\/nu11040753"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Francisqueti, F.V., Minatel, I.O., Ferron, A.J.T., Bazan, S.G.Z., Silva, V.D.S., Garcia, J.L., de Campos, D.H.S., Ferreira, A.L., Moreto, F., and Cicogna, A.C. (2017). Effect of Gamma-Oryzanol as Therapeutic Agent to Prevent Cardiorenal Metabolic Syndrome in Animals Submitted to High Sugar-Fat Diet. Nutrients, 9.","DOI":"10.3390\/nu9121299"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"113981","DOI":"10.1016\/j.fct.2023.113981","article-title":"\u03b3-Oryzanol ameliorates fine dust-induced premature endothelial senescence and dysfunction via attenuating oxidative stress","volume":"179","author":"Shiwakoti","year":"2023","journal-title":"Food Chem. Toxicol."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Goto, S., Rogers, M.A., Blaser, M.C., Higashi, H., Lee, L.H., Schlotter, F., Body, S.C., Aikawa, M., Singh, S.A., and Aikawa, E. (2019). Standardization of Human Calcific Aortic Valve Disease In Vitro Modeling Reveals Passage-Dependent Calcification. Front. Cardiovasc. Med., 6.","DOI":"10.3389\/fcvm.2019.00049"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1186\/s13619-024-00189-8","article-title":"Models for calcific aortic valve disease in vivo and in vitro","volume":"13","author":"Zhu","year":"2024","journal-title":"Cell Regen."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1016\/j.freeradbiomed.2020.04.008","article-title":"Reactive oxygen species (ROS) generation as an underlying mechanism of inorganic phosphate (Pi)-induced mineralization of osteogenic cells","volume":"153","author":"Sana","year":"2020","journal-title":"Free Radic. Biol. Med."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Lin, Y., Zhang, H., Jiang, Y., and Tian, W. (2025). Oxidative stress and its related epigenetic modifications in vascular calcification: Mechanisms and advances. Front. Cardiovasc. Med., 12.","DOI":"10.3389\/fcvm.2025.1662989"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Cabiati, M., Vozzi, F., Ceccherini, E., Guiducci, L., Persiani, E., Gisone, I., Sgalippa, A., Cecchettini, A., and Del Ry, S. (2024). Exploring Bone Morphogenetic Protein-2 and -4 mRNA Expression and Their Receptor Assessment in a Dynamic In Vitro Model of Vascular Calcification. Cells, 13.","DOI":"10.3390\/cells13242091"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1042\/BJ20100357","article-title":"Reactive oxygen species derived from Nox4 mediate BMP2 gene transcription and osteoblast differentiation","volume":"433","author":"Mandal","year":"2011","journal-title":"Biochem. J."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Manzari-Tavakoli, A., Babajani, A., Farjoo, M.H., Hajinasrollah, M., Bahrami, S., and Niknejad, H. (2022). The Cross-Talks Among Bone Morphogenetic Protein (BMP) Signaling and Other Prominent Pathways Involved in Neural Differentiation. Front. Mol. Neurosci., 15.","DOI":"10.3389\/fnmol.2022.827275"},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Huang, R.L., Yuan, Y., Tu, J., Zou, G.M., and Li, Q. (2014). Opposing TNF-\u03b1\/IL-1\u03b2- and BMP-2-activated MAPK signaling pathways converge on Runx2 to regulate BMP-2-induced osteoblastic differentiation. Cell Death Dis., 5.","DOI":"10.1038\/cddis.2014.101"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1038\/s41422-023-00918-9","article-title":"The roles and regulatory mechanisms of TGF-\u03b2 and BMP signaling in bone and cartilage development, homeostasis and disease","volume":"34","author":"Wu","year":"2024","journal-title":"Cell Res."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"659","DOI":"10.1016\/j.jacc.2025.06.049","article-title":"The Pathophysiologic Basis and Management of Calcific Aortic Valve Stenosis: JACC State-of-the-Art Review","volume":"86","author":"Milind","year":"2025","journal-title":"JACC"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"683","DOI":"10.1093\/eurheartj\/ehab757","article-title":"Calcific aortic valve disease: From molecular and cellular mechanisms to medical therapy","volume":"43","author":"Kraler","year":"2021","journal-title":"Eur. Heart J."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1447","DOI":"10.1253\/circj.CJ-24-0706","article-title":"Calcific Aortic Valve Disease\u2015From Mechanism to Treatment\u2015","volume":"89","author":"Chen","year":"2025","journal-title":"Circ. J."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Zhao, Y., Li, H., and Guo, Y. (2025). Interleukin family in vascular calcification: Molecular mechanisms and therapeutic perspectives. Front. Cardiovasc. Med., 12.","DOI":"10.3389\/fcvm.2025.1619018"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"515","DOI":"10.4062\/biomolther.2022.146","article-title":"Niclosamide Inhibits Aortic Valve Interstitial Cell Calcification by Interfering with the GSK-3\u03b2\/\u03b2-Catenin Signaling Pathway","volume":"31","author":"Adhikari","year":"2023","journal-title":"Biomol. Ther."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"e296","DOI":"10.1161\/ATVBAHA.120.315261","article-title":"Secreted Factors from Proinflammatory Macrophages Promote an Osteoblast-Like Phenotype in Valvular Interstitial Cells","volume":"40","author":"Grim","year":"2020","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"e16","DOI":"10.15420\/icr.2024.17","article-title":"Aortic Valve Calcium: A Narrative Review of Its Role in the Assessment of Aortic Stenosis and as a Predictor of Post-transcatheter Aortic Valve Implantation Outcomes","volume":"20","author":"Krzowski","year":"2025","journal-title":"Interv. Cardiol."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Juricic, H., Cuccioloni, M., Bonfili, L., Angeletti, M., Uberti, D., Eleuteri, A.M., Abate, G., and Cecarini, V. (2025). Biochemical, Biological, and Clinical Properties of \u03b3-Oryzanol. Antioxidants, 14.","DOI":"10.3390\/antiox14091099"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"107064","DOI":"10.1016\/j.jff.2025.107064","article-title":"Health properties of \u03b3-oryzanol and its applications: A review","volume":"134","author":"Suphitsara","year":"2025","journal-title":"J. Funct. Foods"},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Chen, L.C., Lai, M.C., Hong, T.Y., and Liu, I.M. (2024). \u03b3-Oryzanol from Rice Bran Antagonizes Glutamate-Induced Excitotoxicity in an In Vitro Model of Differentiated HT-22 Cells. Nutrients, 16.","DOI":"10.3390\/nu16081237"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"3367","DOI":"10.1021\/jf2043407","article-title":"\u03b3-Oryzanol Reduces Adhesion Molecule Expression in Vascular Endothelial Cells via Suppression of Nuclear Factor-\u03baB Activation","volume":"60","author":"Sakai","year":"2012","journal-title":"J. Agric. Food Chem."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"2269","DOI":"10.1007\/s10068-025-01838-7","article-title":"Paeonol from Paeonia lactiflora attenuates calcification of aortic valvular interstitial cell by inhibiting activation of redox-sensitive NF\u03baB\/AKT\/ERK1\/2 pathway","volume":"34","author":"Gwak","year":"2025","journal-title":"Food Sci. Biotechnol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1177\/30494826251344842","article-title":"Comparison of Different Osteogenic Media to Induce Aortic Valve Calcification In Vitro","volume":"2","author":"Evensen","year":"2025","journal-title":"J. Heart Valve Soc."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1007\/s11010-019-03653-1","article-title":"RANKL treatment of vascular endothelial cells leading to paracrine pro-calcific signaling involves ROS production","volume":"464","author":"Harper","year":"2020","journal-title":"Mol. Cell Biochem."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"250","DOI":"10.1016\/j.nefro.2017.07.005","article-title":"Role of pyrophosphate in vascular calcification in chronic kidney disease","volume":"38","author":"Azpiazu","year":"2018","journal-title":"Nefrolog\u00eda"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"410","DOI":"10.1080\/19476337.2023.2210179","article-title":"The antioxidant and antisenescence activities of physically refined rice bran oil surpass those of the combination of \u03b3-oryzanol, \u03b1-tocopherol and sitosterol","volume":"21","author":"Liu","year":"2023","journal-title":"CyTA-J. Food"},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Marques, H.M. (2025). The Bioinorganic Chemistry of the First Row d-Block Metal Ions\u2014An Introduction. Inorganics, 13.","DOI":"10.20944\/preprints202502.0832.v1"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1146\/annurev.bb.21.060192.002301","article-title":"Structure and mechanism of alkaline phosphatase","volume":"21","author":"Coleman","year":"1992","journal-title":"Annu. Rev. Biophys. Biomol. Struct."},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"T\u00f3th, A., Balogh, E., and Jeney, V. (2020). Regulation of Vascular Calcification by Reactive Oxygen Species. Antioxidants, 9.","DOI":"10.3390\/antiox9100963"},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Halloran, D., Durbano, H.W., and Nohe, A. (2020). Bone Morphogenetic Protein-2 in Development and Bone Homeostasis. J. Dev. Biol., 8.","DOI":"10.3390\/jdb8030019"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"115472","DOI":"10.1016\/j.bone.2020.115472","article-title":"Bone morphogenetic protein receptors: Structure, function and targeting by selective small molecule kinase inhibitors","volume":"138","author":"Williams","year":"2020","journal-title":"Bone"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1008","DOI":"10.1016\/j.jtcvs.2009.06.024","article-title":"Bone morphogenic protein 2 induces Runx2 and osteopontin expression in human aortic valve interstitial cells: Role of Smad1 and extracellular signal-regulated kinase 1\/2","volume":"138","author":"Xiaoping","year":"2009","journal-title":"J. Thorac. Cardiovasc. Surg."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1016\/j.bbrc.2017.07.065","article-title":"Evidence for constitutive bone morphogenetic protein-2 secretion by M1 macrophages: Constitutive auto\/paracrine osteogenic signaling by BMP-2 in M1 macrophages","volume":"491","author":"Prabhatchandra","year":"2017","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Niu, Z., Su, G., Li, T., Yu, H., Shen, Y., Zhang, D., and Liu, X. (2022). Vascular Calcification: New Insights into BMP Type I Receptor A. Front. Pharmacol., 13.","DOI":"10.3389\/fphar.2022.887253"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1161","DOI":"10.1016\/j.bbamcr.2007.01.002","article-title":"Regulation of MAPKs by growth factors and receptor tyrosine kinases","volume":"1773","author":"Katz","year":"2007","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1007\/s00018-019-03266-3","article-title":"Smad linker region phosphorylation is a signalling pathway in its own right and not only a modulator of canonical TGF-\u03b2 signalling","volume":"77","author":"Kamato","year":"2020","journal-title":"Cell Mol. Life Sci."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"956","DOI":"10.1016\/j.cellsig.2016.05.002","article-title":"The role of specific Smad linker region phosphorylation in TGF-\u03b2 mediated expression of glycosaminoglycan synthesizing enzymes in vascular smooth muscle","volume":"28","author":"Rostam","year":"2016","journal-title":"Cell. Signal."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1007\/s00109-014-1229-z","article-title":"BMP-2 and TGF-\u03b21 mediate biglycan-induced pro-osteogenic reprogramming in aortic valve interstitial cells","volume":"93","author":"Song","year":"2015","journal-title":"J. Mol. Med."},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Chakrabarti, M., Bhattacharya, A., Gebere, M.G., Johnson, J., Ayub, Z.A., Chatzistamou, I., Vyavahare, N.R., and Azhar, M. (2022). Increased TGF\u03b21 and SMAD3 Contribute to Age-Related Aortic Valve Calcification. Front. Cardiovasc. Med., 9.","DOI":"10.3389\/fcvm.2022.770065"},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Nehl, D., Goody, P.R., Maus, K., Pfeifer, A., Aikawa, E., Bakthiary, F., Zimmer, S., Nickenig, G., Jansen, F., and Hosen, M.R. (2023). Human and porcine aortic valve endothelial and interstitial cell isolation and characterization. Front. Cardiovasc. Med., 10.","DOI":"10.3389\/fcvm.2023.1151028"}],"container-title":["Biomolecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-273X\/16\/1\/107\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,8]],"date-time":"2026-01-08T09:30:01Z","timestamp":1767864601000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-273X\/16\/1\/107"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,8]]},"references-count":64,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,1]]}},"alternative-id":["biom16010107"],"URL":"https:\/\/doi.org\/10.3390\/biom16010107","relation":{},"ISSN":["2218-273X"],"issn-type":[{"value":"2218-273X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,8]]}}}