{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T17:52:06Z","timestamp":1787507526728,"version":"build-2736575974"},"reference-count":67,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2025,11,22]],"date-time":"2025-11-22T00:00:00Z","timestamp":1763769600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000062","name":"National Institutes of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"crossref","award":["1R01DK120866-01"],"award-info":[{"award-number":["1R01DK120866-01"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"crossref"}]},{"name":"National Cancer Institute","award":["R01-CA-221813"],"award-info":[{"award-number":["R01-CA-221813"]}]},{"name":"Advent Health Endowed Chair in Cardiovascular Sciences"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Background\/Objectives: Ponatinib (PON) is a potent anticancer drug widely used to treat chronic myeloid leukemia (CML). Although many cancer survivors benefit from such therapies, managing drug-induced side effects, especially cardiotoxicity, remains a major challenge. Despite its prevalence, the exact mechanisms underlying PON-induced cardiotoxicity have not been thoroughly investigated. Additionally, the potential of Bone Morphogenetic Protein 7 (BMP-7) to alleviate these cardiotoxic effects has yet to be explored. Methods: To address these essential questions, we conducted a study using C57BL\/6 mice. Mice were treated with PON (25 mg\/kg cumulative dosage) or a combination of PON and BMP-7 (600 \u03bcg\/kg), alongside a suitable control group. Heart function was assessed by echocardiography. Different techniques were performed to evaluate the apoptotic pathway. Histological staining was performed to investigate structural changes. Results: PON treatment increased apoptotic cell death (increased expression of BAX and caspase-3) in the heart through the PTEN\/Akt signaling pathway. Further, PON treatment led to increased cardiac hypertrophy, adverse remodeling, and reduced cardiac function. Importantly, BMP-7 markedly reduced PON-induced apoptosis (increased Bcl2 expression) and its downstream effects. Conclusions: These results suggest that BMP-7 might inhibit PON-induced cardiotoxicity. Furthermore, our findings pave the way for future translational studies with BMP-7, which can demonstrate the therapeutic potential of BMP-7 in a clinical setting.<\/jats:p>","DOI":"10.3390\/ph18121776","type":"journal-article","created":{"date-parts":[[2025,11,24]],"date-time":"2025-11-24T10:24:17Z","timestamp":1763979857000},"page":"1776","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["BMP-7 Treatment Ameliorates PTEN-Akt Mediated Apoptosis and Adverse Cardiac Remodeling in Ponatinib-Induced Cardiotoxicity"],"prefix":"10.3390","volume":"18","author":[{"given":"Jonatas M.","family":"Rolando","sequence":"first","affiliation":[{"name":"Division of Metabolic and Cardiovascular Sciences, Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida, Orlando, FL 32816, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5030-2785","authenticated-orcid":false,"given":"Dinender K.","family":"Singla","sequence":"additional","affiliation":[{"name":"Division of Metabolic and Cardiovascular Sciences, Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida, Orlando, FL 32816, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1038\/243290a0","article-title":"Letter: A new consistent chromosomal abnormality in chronic myelogenous leukaemia identified by quinacrine fluorescence and Giemsa staining","volume":"243","author":"Rowley","year":"1973","journal-title":"Nature"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2333","DOI":"10.1038\/sj.onc.1201400","article-title":"The Bcr-Abl tyrosine kinase activates mitogenic signaling pathways and stimulates G1-to-S phase transition in hematopoietic cells","volume":"15","author":"Cortez","year":"1997","journal-title":"Oncogene"},{"key":"ref_3","unstructured":"National Cancer Institute (2025, August 11). Cancer Stat Facts: Leukemia\u2014Chronic Myeloid Leukemia (CML), Available online: https:\/\/seer.cancer.gov\/statfacts\/html\/cmyl.html."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"e468","DOI":"10.1097\/HS9.0000000000000468","article-title":"Chronic Myeloid Leukemia in 2020","volume":"4","author":"Hehlmann","year":"2020","journal-title":"Hemasphere"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1016\/j.leukres.2014.10.005","article-title":"Comparative efficacy of tyrosine kinase inhibitor treatments in the third-line setting, for chronic-phase chronic myelogenous leukemia after failure of second-generation tyrosine kinase inhibitors","volume":"39","author":"Lipton","year":"2015","journal-title":"Leuk. Res."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"104806","DOI":"10.1016\/j.critrevonc.2025.104806","article-title":"Comparison of third-generation tyrosine kinase inhibitor (TKI) ponatinib with first- and second-generation TKIs for treatment of Philadelphia chromosome-positive acute lymphoblastic leukemia: A systematic review and bias-corrected meta-analysis","volume":"213","author":"Raza","year":"2025","journal-title":"Crit. Rev. Oncol.\/Hematol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"103675","DOI":"10.1016\/j.htct.2024.04.124","article-title":"Ponatinib in the treatment of patients with chronic myeloid leukemia and increased cardiovascular risk: A review of management strategies","volume":"47","author":"Sacha","year":"2025","journal-title":"Hematol. Transfus. Cell Ther."},{"key":"ref_8","unstructured":"Agrawal, D.K., \u0160krbi\u0107, R., Stojiljkovi\u0107, M.P., and Djuric, D.M. (2025). Ponatinib in Chronic Myeloid Leukemia and Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia: Efficacy, Mechanisms, and Cardiotoxic Challenges. Cardiovascular Toxicity: Incidence, Pathogenesis and Treatment Strategies, Springer Nature."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"S573","DOI":"10.1016\/S2152-2650(25)01949-4","article-title":"CML-663: Cardiotoxicity in Chronic Myeloid Leukemia: Ponatinib-Induced Cardiomyopathy","volume":"25","author":"Egwuonwu","year":"2025","journal-title":"Clin. Lymphoma Myeloma Leuk."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1038\/s41698-017-0034-x","article-title":"Precision cardio-oncology: Understanding the cardiotoxicity of cancer therapy","volume":"1","author":"Han","year":"2017","journal-title":"npj Precis. Oncol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"115361","DOI":"10.1016\/j.addr.2024.115361","article-title":"Navigating cancer therapy induced cardiotoxicity: From pathophysiology to treatment innovations","volume":"211","author":"Jensen","year":"2024","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1161\/CIRCRESAHA.122.321504","article-title":"Ponatinib Drives Cardiotoxicity by S100A8\/A9-NLRP3-IL-1\u03b2 Mediated Inflammation","volume":"132","author":"Tousif","year":"2023","journal-title":"Circ. Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"482","DOI":"10.1161\/CIRCRESAHA.123.323683","article-title":"Integrated Stress Response Potentiates Ponatinib-Induced Cardiotoxicity","volume":"134","author":"Yan","year":"2024","journal-title":"Circ. Res."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Mattii, L., Moscato, S., Ippolito, C., Polizzi, E., Novo, G., Zucchi, R., De Caterina, R., Ghelardoni, S., and Madonna, R. (2024). Empagliflozin mitigates ponatinib-induced cardiotoxicity by restoring the connexin 43-autophagy pathway. Biomed. Pharmacother., 178.","DOI":"10.1016\/j.biopha.2024.117278"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Wang, H., Wang, Y., Li, J., He, Z., Boswell, S.A., Chung, M., You, F., and Han, S. (2023). Three tyrosine kinase inhibitors cause cardiotoxicity by inducing endoplasmic reticulum stress and inflammation in cardiomyocytes. BMC Med., 21.","DOI":"10.1186\/s12916-023-02838-2"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1080\/01926230701320337","article-title":"Apoptosis: A review of programmed cell death","volume":"35","author":"Elmore","year":"2007","journal-title":"Toxicol. Pathol."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Mustafa, M., Ahmad, R., Tantry, I.Q., Ahmad, W., Siddiqui, S., Alam, M., Abbas, K., Hassan, M.I., and Habib, S. (2024). Apoptosis: A Comprehensive Overview of Signaling Pathways, Morphological Changes, and Physiological Significance and Therapeutic Implications. Cells, 13.","DOI":"10.3390\/cells13221838"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"205","DOI":"10.15171\/apb.2019.024","article-title":"Understanding Apoptosis and Apoptotic Pathways Targeted Cancer Therapeutics","volume":"9","author":"Jan","year":"2019","journal-title":"Adv. Pharm. Bull."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"480","DOI":"10.1136\/heart.87.5.480","article-title":"Apoptosis in the cardiovascular system","volume":"87","author":"Bennett","year":"2002","journal-title":"Heart"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"933","DOI":"10.1016\/j.molcel.2022.01.008","article-title":"The interplay between BAX and BAK tunes apoptotic pore growth to control mitochondrial-DNA-mediated inflammation","volume":"82","author":"Cosentino","year":"2022","journal-title":"Mol. Cell"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1038\/s41580-018-0089-8","article-title":"Regulation of apoptosis in health and disease: The balancing act of BCL-2 family proteins","volume":"20","author":"Singh","year":"2019","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Merino, H., and Singla, D.K. (2014). Notch-1 mediated cardiac protection following embryonic and induced pluripotent stem cell transplantation in doxorubicin-induced heart failure. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0101024"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"H1236","DOI":"10.1152\/ajpheart.00121.2018","article-title":"PTEN inhibitor VO-OHpic attenuates inflammatory M1 macrophages and cardiac remodeling in doxorubicin-induced cardiomyopathy","volume":"315","author":"Johnson","year":"2018","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"966","DOI":"10.1093\/cvr\/cvz006","article-title":"Ponatinib-induced cardiotoxicity: Delineating the signalling mechanisms and potential rescue strategies","volume":"115","author":"Singh","year":"2019","journal-title":"Cardiovasc. Res."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"112466","DOI":"10.1016\/j.msec.2021.112466","article-title":"FDA-approved bone grafts and bone graft substitute devices in bone regeneration","volume":"130","author":"Gillman","year":"2021","journal-title":"Mater. Sci. Eng. C"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1177\/1558944721990805","article-title":"Bone Morphogenic Protein for Upper Extremity Fractures: A Systematic Review","volume":"18","author":"Sandler","year":"2023","journal-title":"Hand"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"H762","DOI":"10.1152\/ajpheart.00367.2014","article-title":"BMP-7 attenuates adverse cardiac remodeling mediated through M2 macrophages in prediabetic cardiomyopathy","volume":"307","author":"Urbina","year":"2014","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Elmadbouh, I., and Singla, D.K. (2021). BMP-7 Attenuates Inflammation-Induced Pyroptosis and Improves Cardiac Repair in Diabetic Cardiomyopathy. Cells, 10.","DOI":"10.3390\/cells10102640"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1031","DOI":"10.3727\/096368914X679200","article-title":"Akt-mTOR Pathway Inhibits Apoptosis and Fibrosis in Doxorubicin-Induced Cardiotoxicity Following Embryonic Stem Cell Transplantation","volume":"24","author":"Singla","year":"2015","journal-title":"Cell Transpl."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2339","DOI":"10.1016\/j.celrep.2018.10.103","article-title":"The Mitochondrial Apoptotic Effectors BAX\/BAK Activate Caspase-3 and -7 to Trigger NLRP3 Inflammasome and Caspase-8 Driven IL-1\u03b2 Activation","volume":"25","author":"Vince","year":"2018","journal-title":"Cell Rep."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1046\/j.0022-202x.2001.01409.x","article-title":"The Bax\/Bcl-2 Ratio Determines the Susceptibility of Human Melanoma Cells to CD95\/Fas-Mediated Apoptosis","volume":"117","author":"Raisova","year":"2001","journal-title":"J. Investig. Dermatol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1177\/1074248415624158","article-title":"The PTEN\/Akt Signaling Pathway Mediates Myocardial Apoptosis in Swine After Coronary Microembolization","volume":"21","author":"Wang","year":"2016","journal-title":"J. Cardiovasc. Pharmacol. Ther."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1016\/j.hfc.2011.08.010","article-title":"Role of apoptosis in adverse ventricular remodeling","volume":"8","author":"Abbate","year":"2012","journal-title":"Heart Fail. Clin."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1016\/j.jcmg.2010.10.008","article-title":"Left Ventricular Remodeling in Heart Failure: Current Concepts in Clinical Significance and Assessment","volume":"4","author":"Konstam","year":"2011","journal-title":"JACC Cardiovasc. Imaging"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1783","DOI":"10.1056\/NEJMoa1306494","article-title":"A phase 2 trial of ponatinib in Philadelphia chromosome-positive leukemias","volume":"369","author":"Cortes","year":"2013","journal-title":"N. Engl. J. Med."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"6503","DOI":"10.1200\/jco.2012.30.15_suppl.6503","article-title":"PACE: A pivotal phase II trial of ponatinib in patients with CML and Ph+ALL resistant or intolerant to dasatinib or nilotinib, or with the T315I mutation","volume":"30","author":"Cortes","year":"2012","journal-title":"J. Clin. Oncol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"530","DOI":"10.1182\/bloodadvances.2019000268","article-title":"Side-effects profile and outcomes of ponatinib in the treatment of chronic myeloid leukemia","volume":"4","author":"Chan","year":"2020","journal-title":"Blood Adv."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1038\/s41580-023-00689-6","article-title":"A guide to cell death pathways","volume":"25","author":"Yuan","year":"2023","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1380","DOI":"10.1111\/jcmm.17008","article-title":"Sex-related differential susceptibility to ponatinib cardiotoxicity and differential modulation of the Notch1 signalling pathway in a murine model","volume":"26","author":"Madonna","year":"2022","journal-title":"J. Cell. Mol. Med."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1166","DOI":"10.1038\/sj.cdd.4400783","article-title":"Pro-apoptotic cascade activates BID, which oligomerizes BAK or BAX into pores that result in the release of cytochrome c","volume":"7","author":"Korsmeyer","year":"2000","journal-title":"Cell Death Differ."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Wolf, P., Schoeniger, A., and Edlich, F. (2022). Pro-apoptotic complexes of BAX and BAK on the outer mitochondrial membrane. Biochim. Biophys. Acta Mol. Cell Res., 1869.","DOI":"10.1016\/j.bbamcr.2022.119317"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1099","DOI":"10.1093\/molehr\/4.12.1099","article-title":"The relationship between BcI2, Bax and p53: Consequences for cell cycle progression and cell death","volume":"4","author":"Basu","year":"1998","journal-title":"Mol. Hum. Reprod."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Wang, Q., Zhang, L., Yuan, X., Ou, Y., Zhu, X., Cheng, Z., Zhang, P., Wu, X., Meng, Y., and Zhang, L. (2016). The Relationship between the Bcl-2\/Bax Proteins and the Mitochondria-Mediated Apoptosis Pathway in the Differentiation of Adipose-Derived Stromal Cells into Neurons. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0163327"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1038\/s41419-018-0408-1","article-title":"Cytochrome c speeds up caspase cascade activation by blocking 14-3-3\u03b5-dependent Apaf-1 inhibition","volume":"9","year":"2018","journal-title":"Cell Death Dis."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1170","DOI":"10.1177\/1947601911407325","article-title":"PTEN Tumor Suppressor Network in PI3K-Akt Pathway Control","volume":"1","author":"Georgescu","year":"2010","journal-title":"Genes Cancer"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"708","DOI":"10.1016\/j.molcel.2021.01.033","article-title":"Regulation of PTEN translation by PI3K signaling maintains pathway homeostasis","volume":"81","author":"Mukherjee","year":"2021","journal-title":"Mol. Cell"},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Schlittler, M., Pramstaller, P.P., Rossini, A., and De Bortoli, M. (2023). Myocardial Fibrosis in Hypertrophic Cardiomyopathy: A Perspective from Fibroblasts. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms241914845"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/j.cardiores.2005.04.012","article-title":"Myocyte apoptosis in heart failure","volume":"67","author":"Bertrand","year":"2005","journal-title":"Cardiovasc. Res."},{"key":"ref_49","unstructured":"Takeda Pharmaceuticals America (2025, August 11). ICLUSIG\u00ae\u00ae (ponatinib) Tablets for Oral Use. Available online: https:\/\/www.iclusig.com\/sites\/default\/files\/2023-02\/iclusig-prescribing-information.pdf."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Madonna, R., Moscato, S., Polizzi, E., Pieragostino, D., Cufaro, M.C., Del Boccio, P., Bianchi, F., De Caterina, R., and Mattii, L. (2021). Connexin 43 and Connexin 26 Involvement in the Ponatinib-Induced Cardiomyopathy: Sex-Related Differences in a Murine Model. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22115815"},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Smoljan, I., Detel, D., Buljevic, S., Erjavec, I., and Mari\u0107, I. (2023). Therapeutic Potential of BMP7 in the Treatment of Osteoporosis Caused by the Interaction between Inflammation and Corticosteroids in Inflammatory Bowel Disease. Biomedicines, 11.","DOI":"10.3390\/biomedicines11082161"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1167\/iovs.63.6.7","article-title":"Potential Therapeutic Role of Bone Morphogenic Protein 7 (BMP7) in the Pathogenesis of Graves\u2019 Orbitopathy","volume":"63","author":"Kim","year":"2022","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Narasimhulu, C.A., and Singla, D.K. (2020). The Role of Bone Morphogenetic Protein 7 (BMP-7) in Inflammation in Heart Diseases. Cells, 9.","DOI":"10.3390\/cells9020280"},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Narasimhulu, C.A., and Singla, D.K. (2023). BMP-7 Attenuates Sarcopenia and Adverse Muscle Remodeling in Diabetic Mice via Alleviation of Lipids, Inflammation, HMGB1, and Pyroptosis. Antioxidants, 12.","DOI":"10.3390\/antiox12020331"},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Takano, M., Toda, S., Watanabe, H., Fujimura, R., Nishida, K., Bi, J., Minayoshi, Y., Miyahisa, M., Maeda, H., and Maruyama, T. (2022). Engineering of a Long-Acting Bone Morphogenetic Protein-7 by Fusion with Albumin for the Treatment of Renal Injury. Pharmaceutics, 14.","DOI":"10.3390\/pharmaceutics14071334"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"254","DOI":"10.1038\/s41419-022-04529-x","article-title":"BMP-7 ameliorates partial epithelial-mesenchymal transition by restoring SnoN protein level via Smad1\/5 pathway in diabetic kidney disease","volume":"13","author":"Peng","year":"2022","journal-title":"Cell Death Dis."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"558","DOI":"10.1161\/01.STR.0000051507.64423.00","article-title":"Intravenous Administration of Bone Morphogenetic Protein-7 After Ischemia Improves Motor Function in Stroke Rats","volume":"34","author":"Chang","year":"2003","journal-title":"Stroke"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"e15","DOI":"10.1093\/brain\/awaa368","article-title":"BMP5\/7 protect dopaminergic neurons in an \u03b1-synuclein mouse model of Parkinson\u2019s disease","volume":"144","author":"Vitic","year":"2021","journal-title":"Brain"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"540","DOI":"10.4103\/0019-5413.121569","article-title":"Bone morphogenetic protein-7 accelerates fracture healing in osteoporotic rats","volume":"47","author":"Diwan","year":"2013","journal-title":"Indian J. Orthop."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"626","DOI":"10.1111\/j.1445-2197.2007.04175.x","article-title":"Bone morphogenetic proteins in clinical applications","volume":"77","author":"Gautschi","year":"2007","journal-title":"ANZ J. Surg."},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Hunter, D.J., Pike, M.C., Jonas, B.L., Kissin, E., Krop, J., and McAlindon, T. (2010). Phase 1 safety and tolerability study of BMP-7 in symptomatic knee osteoarthritis. BMC Musculoskelet. Disord., 11.","DOI":"10.1186\/1471-2474-11-232"},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Tate, M., Perera, N., Prakoso, D., Willis, A.M., Deo, M., Oseghale, O., Qian, H., Donner, D.G., Kiriazis, H., and De Blasio, M.J. (2021). Bone Morphogenetic Protein 7 Gene Delivery Improves Cardiac Structure and Function in a Murine Model of Diabetic Cardiomyopathy. Front. Pharmacol., 12.","DOI":"10.3389\/fphar.2021.719290"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"e15629","DOI":"10.14814\/phy2.15629","article-title":"PTEN-AKT pathway attenuates apoptosis and adverse remodeling in ponatinib-induced skeletal muscle toxicity following BMP-7 treatment","volume":"11","author":"Srivastava","year":"2023","journal-title":"Physiol. Rep."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1139\/cjpp-2021-0596","article-title":"Doxorubicin-induced apoptosis enhances monocyte infiltration and adverse cardiac remodeling in diabetic animals","volume":"100","author":"Narasimhulu","year":"2022","journal-title":"Can. J. Physiol. Pharmacol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"6043064","DOI":"10.1155\/2018\/6043064","article-title":"Secreted Frizzled-Related Protein-2 Inhibits Doxorubicin-Induced Apoptosis Mediated through the Akt-mTOR Pathway in Soleus Muscle","volume":"2018","author":"Merino","year":"2018","journal-title":"Oxidative Med. Cell. Longev."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"H1308","DOI":"10.1152\/ajpheart.01277.2006","article-title":"Transplanted embryonic stem cells following mouse myocardial infarction inhibit apoptosis and cardiac remodeling","volume":"293","author":"Singla","year":"2007","journal-title":"Am. J. Physiol.-Heart Circ. Physiol."},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Singla, D.K., Johnson, T.A., and Dargani, Z.T. (2019). Exosome Treatment Enhances Anti-Inflammatory M2 Macrophages and Reduces Inflammation-Induced Pyroptosis in Doxorubicin-Induced Cardiomyopathy. Cells, 8.","DOI":"10.3390\/cells8101224"}],"container-title":["Pharmaceuticals"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1424-8247\/18\/12\/1776\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,26]],"date-time":"2025-11-26T05:18:15Z","timestamp":1764134295000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1424-8247\/18\/12\/1776"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,22]]},"references-count":67,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["ph18121776"],"URL":"https:\/\/doi.org\/10.3390\/ph18121776","relation":{},"ISSN":["1424-8247"],"issn-type":[{"value":"1424-8247","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,11,22]]}}}