{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T04:19:47Z","timestamp":1790741987042,"version":"4.1.0"},"reference-count":47,"publisher":"Springer Science and Business Media LLC","issue":"11-12","license":[{"start":{"date-parts":[[2025,9,25]],"date-time":"2025-09-25T00:00:00Z","timestamp":1758758400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,9,25]],"date-time":"2025-09-25T00:00:00Z","timestamp":1758758400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100014584","name":"Universit\u00e4tsmedizin der Johannes Gutenberg-Universit\u00e4t Mainz","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100014584","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Mol Med"],"published-print":{"date-parts":[[2025,11]]},"abstract":"<jats:sec>\n                    <jats:title>Abstract<\/jats:title>\n                    <jats:p>\n                      This study investigates the potential of nintedanib, a tyrosine kinase inhibitor with antifibrotic and anti-inflammatory properties, to mitigate post-traumatic joint contracture (PTJC) in a rat model. Given the lack of effective pharmacological treatments for this debilitating condition, this study aims to address the unmet need for non-surgical interventions by targeting the underlying fibrotic and inflammatory processes. A total of 26 male Sprague\u2013Dawley rats were subjected to standardized knee trauma and immobilization for 2\u00a0weeks. Rats were randomized into two groups: a nintedanib treatment group (5\u00a0mg\/kg taken twice daily,\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200913) and a placebo group (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200913). Joint mobility was evaluated biomechanically by measuring the contracture angle (CA) and resistance to extension. Posterior joint capsule tissues were analyzed histologically and via qPCR for profibrotic gene expression, including\n                      <jats:italic>\u03b1-Sma<\/jats:italic>\n                      ,\n                      <jats:italic>Il-6<\/jats:italic>\n                      ,\n                      <jats:italic>Tgf-\u03b21<\/jats:italic>\n                      ,\n                      <jats:italic>Nf-\u03bab<\/jats:italic>\n                      , and\n                      <jats:italic>Ctgf<\/jats:italic>\n                      . Nintedanib treatment significantly reduced CA compared to placebo (68.1\u00b0\u2009\u00b1\u200912.6\u00b0 vs. 84.8\u00b0\u2009\u00b1\u200911.1\u00b0,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.01), indicating improved joint mobility. Knee extension in the nintedanib-treated rats required less force, particularly at lower extension angles (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.05). Molecular analysis showed a marked reduction in\n                      <jats:italic>\u03b1-Sma<\/jats:italic>\n                      expression, a myofibroblast marker, in the nintedanib group compared to placebo (11-fold decrease,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.05). Histological examinations revealed relatively fewer myofibroblasts in the posterior joint capsule of rats treated with nintedanib. Nintedanib effectively mitigates fibrosis and inflammation in a rat model of PTJC, enhancing joint mobility and reducing profibrotic gene expression. These findings support further exploration of nintedanib as a pharmacological therapy for PTJC in clinical settings.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key messages<\/jats:title>\n                    <jats:p>\n                      <jats:list list-type=\"bullet\">\n                        <jats:list-item>\n                          <jats:p>Nintedanib is a promising candidate for the prevention of post-traumatic joint contracture.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Oral administration of nintedanib (5\u00a0mg twice daily) over a period of 2\u00a0weeks improves joint mobility in post-traumatic joint contracture (PTJC).<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Nintedanib reduces the relative number of myofibroblasts.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>\n                            A significant reduction in\n                            <jats:italic>\u03b1-SMA<\/jats:italic>\n                            expression levels under the influence of nintedanib indicates a slowed transition of fibroblasts to myofibroblasts.\n                          <\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s00109-025-02593-2","type":"journal-article","created":{"date-parts":[[2025,9,24]],"date-time":"2025-09-24T23:19:19Z","timestamp":1758755959000},"page":"1461-1474","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Nintedanib reduces severity of post-traumatic joint contracture by modulating fibrosis and inflammation"],"prefix":"10.1007","volume":"103","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-7299-4170","authenticated-orcid":false,"given":"Erik","family":"Wegner","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dennis","family":"Warnke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victoria","family":"Buschmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benedikt","family":"Hild","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Berenika","family":"Mais","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulrike","family":"Ritz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Austin","family":"Harper","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erol","family":"Gercek","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philipp","family":"Drees","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Baranowski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,9,25]]},"reference":[{"issue":"1","key":"2593_CR1","doi-asserted-by":"publisher","first-page":"38","DOI":"10.1177\/1758573218793903","volume":"12","author":"D Zhang","year":"2020","unstructured":"Zhang D, Nazarian A, Rodriguez EK (2020) Post-traumatic elbow stiffness: pathogenesis and current treatments. Shoulder Elbow 12(1):38\u201345","journal-title":"Shoulder Elbow"},{"key":"2593_CR2","doi-asserted-by":"publisher","first-page":"125","DOI":"10.1016\/j.jcot.2021.05.006","volume":"19","author":"A Akhtar","year":"2021","unstructured":"Akhtar A, Hughes B, Watts AC (2021) The post-traumatic stiff elbow: a review. J Clin Orthop Trauma 19:125\u2013131","journal-title":"J Clin Orthop Trauma"},{"key":"2593_CR3","first-page":"26","volume":"431","author":"BF Morrey","year":"2005","unstructured":"Morrey BF (2005) The posttraumatic stiff elbow. Clin Orthop Relat Res 431:26\u201335","journal-title":"Clin Orthop Relat Res"},{"key":"2593_CR4","doi-asserted-by":"publisher","DOI":"10.3389\/fmed.2020.604056","volume":"7","author":"Y Qian","year":"2020","unstructured":"Qian Y, Yu S, Shi Y, Huang H, Fan C (2020) Risk factors for the occurrence and progression of posttraumatic elbow stiffness: a case-control study of 688 cases. Front Med 7:604056","journal-title":"Front Med"},{"issue":"3","key":"2593_CR5","first-page":"269","volume":"51","author":"U Fischer","year":"2015","unstructured":"Fischer U, Muller M, Strobl R, Bartoszek G, Meyer G, Grill E (2015) Prevalence of functioning and disability in older patients with joint contractures: a cross-sectional study. Eur J Phys Rehabil Med 51(3):269\u2013279","journal-title":"Eur J Phys Rehabil Med"},{"key":"2593_CR6","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1038\/s41413-019-0047-x","volume":"7","author":"KM Usher","year":"2019","unstructured":"Usher KM, Zhu S, Mavropalias G, Carrino JA, Zhao J, Xu J (2019) Pathological mechanisms and therapeutic outlooks for arthrofibrosis. Bone Res 7:9","journal-title":"Bone Res"},{"issue":"11","key":"2593_CR7","doi-asserted-by":"publisher","first-page":"1520","DOI":"10.1002\/jor.22700","volume":"32","author":"W Efird","year":"2014","unstructured":"Efird W, Kellam P, Yeazell S, Weinhold P, Dahners LE (2014) An evaluation of prophylactic treatments to prevent post traumatic joint stiffness. J Orthop Res 32(11):1520\u20131524","journal-title":"J Orthop Res"},{"issue":"1","key":"2593_CR8","doi-asserted-by":"publisher","first-page":"446","DOI":"10.1186\/s12891-016-1303-5","volume":"17","author":"J Ozawa","year":"2016","unstructured":"Ozawa J, Kaneguchi A, Tanaka R, Kito N, Moriyama H (2016) Cyclooxygenase-2 inhibitor celecoxib attenuates joint contracture following immobilization in rat knees. BMC Musculoskelet Disord 17(1):446","journal-title":"BMC Musculoskelet Disord"},{"issue":"4","key":"2593_CR9","doi-asserted-by":"publisher","first-page":"1409","DOI":"10.1007\/s10753-018-0788-5","volume":"41","author":"A Kaneguchi","year":"2018","unstructured":"Kaneguchi A, Ozawa J, Yamaoka K (2018) Anti-inflammatory drug dexamethasone treatment during the remobilization period improves range of motion in a rat knee model of joint contracture. Inflammation 41(4):1409\u20131423","journal-title":"Inflammation"},{"issue":"6","key":"2593_CR10","doi-asserted-by":"publisher","first-page":"1468","DOI":"10.2106\/JBJS.I.00684","volume":"92","author":"MJ Monument","year":"2010","unstructured":"Monument MJ, Hart DA, Befus AD, Salo PT, Zhang M, Hildebrand KA (2010) The mast cell stabilizer ketotifen fumarate lessens contracture severity and myofibroblast hyperplasia: a study of a rabbit model of posttraumatic joint contractures. J Bone Joint Surg Am 92(6):1468\u20131477","journal-title":"J Bone Joint Surg Am"},{"issue":"6","key":"2593_CR11","doi-asserted-by":"publisher","first-page":"L998","DOI":"10.1152\/ajplung.00304.2017","volume":"314","author":"EF Redente","year":"2018","unstructured":"Redente EF, Aguilar MA, Black BP, Edelman BL, Bahadur AN, Humphries SM et al (2018) Nintedanib reduces pulmonary fibrosis in a model of rheumatoid arthritis-associated interstitial lung disease. Am J Physiol Lung Cell Mol Physiol 314(6):L998\u2013L1009","journal-title":"Am J Physiol Lung Cell Mol Physiol"},{"issue":"9","key":"2593_CR12","doi-asserted-by":"publisher","first-page":"2311","DOI":"10.1007\/s10067-023-06623-7","volume":"42","author":"EL Matteson","year":"2023","unstructured":"Matteson EL, Aringer M, Burmester GR, Mueller H, Moros L, Kolb M (2023) Effect of nintedanib in patients with progressive pulmonary fibrosis associated with rheumatoid arthritis: data from the INBUILD trial. Clin Rheumatol 42(9):2311\u20132319","journal-title":"Clin Rheumatol"},{"issue":"1","key":"2593_CR13","doi-asserted-by":"publisher","first-page":"18939","DOI":"10.1038\/s41598-024-69080-5","volume":"14","author":"Z Wei","year":"2024","unstructured":"Wei Z, Chen X, Sun Y, Zhang Y, Dong R, Wang X et al (2024) Exploring the molecular mechanisms and shared potential drugs between rheumatoid arthritis and arthrofibrosis based on large language model and synovial microenvironment analysis. Sci Rep 14(1):18939","journal-title":"Sci Rep"},{"issue":"9","key":"2593_CR14","doi-asserted-by":"publisher","first-page":"1131","DOI":"10.1007\/s40262-019-00766-0","volume":"58","author":"S Wind","year":"2019","unstructured":"Wind S, Schmid U, Freiwald M, Marzin K, Lotz R, Ebner T et al (2019) Clinical pharmacokinetics and pharmacodynamics of nintedanib. Clin Pharmacokinet 58(9):1131\u20131147","journal-title":"Clin Pharmacokinet"},{"issue":"5","key":"2593_CR15","doi-asserted-by":"publisher","first-page":"1434","DOI":"10.1183\/09031936.00174914","volume":"45","author":"L Wollin","year":"2015","unstructured":"Wollin L, Wex E, Pautsch A, Schnapp G, Hostettler KE, Stowasser S et al (2015) Mode of action of nintedanib in the treatment of idiopathic pulmonary fibrosis. Eur Respir J 45(5):1434\u20131445","journal-title":"Eur Respir J"},{"issue":"4","key":"2593_CR16","doi-asserted-by":"publisher","first-page":"1340","DOI":"10.1016\/j.ajpath.2012.02.004","volume":"180","author":"B Hinz","year":"2012","unstructured":"Hinz B, Phan SH, Thannickal VJ, Prunotto M, Desmouliere A, Varga J et al (2012) Recent developments in myofibroblast biology: paradigms for connective tissue remodeling. Am J Pathol 180(4):1340\u20131355","journal-title":"Am J Pathol"},{"key":"2593_CR17","doi-asserted-by":"publisher","DOI":"10.1177\/1759720X211060907","volume":"13","author":"EM Wilfong","year":"2021","unstructured":"Wilfong EM, Aggarwal R (2021) Role of antifibrotics in the management of idiopathic inflammatory myopathy associated interstitial lung disease. Ther Adv Musculoskelet Dis 13:1759720X211060907","journal-title":"Ther Adv Musculoskelet Dis"},{"key":"2593_CR18","unstructured":"Ofev (nintedanib) (2015) An overview of Ofev and why it is authorised in the EU, European\u00a0Medicines Agency. https:\/\/www.ema.europa.eu\/en\/documents\/overview\/ofev-epar-medicines-overview_en.pdf.\u00a0Accessed 13 Mar 2025"},{"issue":"1","key":"2593_CR19","doi-asserted-by":"publisher","first-page":"185","DOI":"10.1186\/s13018-018-0894-y","volume":"13","author":"A Baranowski","year":"2018","unstructured":"Baranowski A, Schlemmer L, Forster K, Mattyasovszky SG, Ritz U, Wagner D et al (2018) A novel rat model of stable posttraumatic joint stiffness of the knee. J Orthop Surg Res 13(1):185","journal-title":"J Orthop Surg Res"},{"issue":"1","key":"2593_CR20","doi-asserted-by":"publisher","first-page":"6","DOI":"10.1016\/S0003-9993(00)90213-2","volume":"81","author":"G Trudel","year":"2000","unstructured":"Trudel G, Uhthoff HK (2000) Contractures secondary to immobility: is the restriction articular or muscular? An experimental longitudinal study in the rat knee. Arch Phys Med Rehabil 81(1):6\u201313","journal-title":"Arch Phys Med Rehabil"},{"issue":"6","key":"2593_CR21","doi-asserted-by":"publisher","first-page":"887","DOI":"10.1115\/1.1634285","volume":"125","author":"KA Hildebrand","year":"2003","unstructured":"Hildebrand KA, Holmberg M, Shrive N (2003) A new method to measure post-traumatic joint contractures in the rabbit knee. J Biomech Eng 125(6):887\u2013892","journal-title":"J Biomech Eng"},{"issue":"8","key":"2593_CR22","doi-asserted-by":"publisher","first-page":"1028","DOI":"10.1002\/jor.20845","volume":"27","author":"S Nesterenko","year":"2009","unstructured":"Nesterenko S, Morrey ME, Abdel MP, An KN, Steinmann SP, Morrey BF et al (2009) New rabbit knee model of posttraumatic joint contracture: indirect capsular damage induces a severe contracture. J Orthop Res 27(8):1028\u20131032","journal-title":"J Orthop Res"},{"issue":"2","key":"2593_CR23","doi-asserted-by":"publisher","first-page":"354","DOI":"10.1002\/jor.22981","volume":"34","author":"SP Lake","year":"2016","unstructured":"Lake SP, Castile RM, Borinsky S, Dunham CL, Havlioglu N, Galatz LM (2016) Development and use of an animal model to study post-traumatic stiffness and contracture of the elbow. J Orthop Res 34(2):354\u2013364","journal-title":"J Orthop Res"},{"key":"2593_CR24","doi-asserted-by":"publisher","first-page":"2603","DOI":"10.2147\/DDDT.S204135","volume":"13","author":"A Baranowski","year":"2019","unstructured":"Baranowski A, Schlemmer L, Forster K, Slotina E, Mickan T, Truffel S et al (2019) Effects of losartan and atorvastatin on the development of early posttraumatic joint stiffness in a rat model. Drug Des Devel Ther 13:2603\u20132618","journal-title":"Drug Des Devel Ther"},{"issue":"3","key":"2593_CR25","doi-asserted-by":"publisher","first-page":"985","DOI":"10.1016\/S0002-9440(10)64920-6","volume":"160","author":"S Morikawa","year":"2002","unstructured":"Morikawa S, Baluk P, Kaidoh T, Haskell A, Jain RK, McDonald DM (2002) Abnormalities in pericytes on blood vessels and endothelial sprouts in tumors. Am J Pathol 160(3):985\u20131000","journal-title":"Am J Pathol"},{"key":"2593_CR26","doi-asserted-by":"publisher","DOI":"10.3390\/pharmaceutics14030523","author":"E Wegner","year":"2022","unstructured":"Wegner E, Slotina E, Mickan T, Truffel S, Arand C, Wagner D et al (2022) Pleiotropic long-term effects of atorvastatin on posttraumatic joint contracture in a rat model. Pharmaceutics. https:\/\/doi.org\/10.3390\/pharmaceutics14030523","journal-title":"Pharmaceutics"},{"key":"2593_CR27","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2023.115291","volume":"166","author":"E Wegner","year":"2023","unstructured":"Wegner E, Mickan T, Truffel S, Slotina E, Muller L, Wunderlich F et al (2023) The effect of losartan on the development of post-traumatic joint stiffness in a rat model. Biomed Pharmacother 166:115291","journal-title":"Biomed Pharmacother"},{"issue":"18","key":"2593_CR28","doi-asserted-by":"publisher","first-page":"1718","DOI":"10.1056\/NEJMoa1908681","volume":"381","author":"KR Flaherty","year":"2019","unstructured":"Flaherty KR, Wells AU, Cottin V, Devaraj A, Walsh SLF, Inoue Y et al (2019) Nintedanib in progressive fibrosing interstitial lung diseases. N Engl J Med 381(18):1718\u20131727","journal-title":"N Engl J Med"},{"issue":"9","key":"2593_CR29","doi-asserted-by":"publisher","first-page":"2730","DOI":"10.1091\/mbc.12.9.2730","volume":"12","author":"B Hinz","year":"2001","unstructured":"Hinz B, Celetta G, Tomasek JJ, Gabbiani G, Chaponnier C (2001) Alpha-smooth muscle actin expression upregulates fibroblast contractile activity. Mol Biol Cell 12(9):2730\u20132741","journal-title":"Mol Biol Cell"},{"issue":"12","key":"2593_CR30","doi-asserted-by":"publisher","first-page":"705","DOI":"10.1038\/s41584-019-0322-7","volume":"15","author":"JHW Distler","year":"2019","unstructured":"Distler JHW, Gyorfi AH, Ramanujam M, Whitfield ML, Konigshoff M, Lafyatis R (2019) Shared and distinct mechanisms of fibrosis. Nat Rev Rheumatol 15(12):705\u2013730","journal-title":"Nat Rev Rheumatol"},{"issue":"17","key":"2593_CR31","doi-asserted-by":"publisher","first-page":"1581","DOI":"10.1007\/s40265-023-01950-0","volume":"83","author":"F Bonella","year":"2023","unstructured":"Bonella F, Spagnolo P, Ryerson C (2023) Current and future treatment landscape for idiopathic pulmonary fibrosis. Drugs 83(17):1581\u20131593","journal-title":"Drugs"},{"key":"2593_CR32","doi-asserted-by":"publisher","first-page":"1759720X2210744","DOI":"10.1177\/1759720X221074457","volume":"14","author":"M Liang","year":"2022","unstructured":"Liang M, Matteson EL, Abril A, Distler JHW (2022) The role of antifibrotics in the treatment of rheumatoid arthritis-associated interstitial lung disease. Ther Adv Musculoskelet Dis. 14:1759720X221074457","journal-title":"Ther Adv Musculoskelet Dis."},{"issue":"7","key":"2593_CR33","doi-asserted-by":"publisher","first-page":"e1900223","DOI":"10.2106\/JBJS.RVW.19.00223","volume":"8","author":"IO Ibrahim","year":"2020","unstructured":"Ibrahim IO, Nazarian A, Rodriguez EK (2020) Clinical management of arthrofibrosis: state of the art and therapeutic outlook. JBJS Rev 8(7):e1900223","journal-title":"JBJS Rev"},{"key":"2593_CR34","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1016\/j.gene.2017.01.025","volume":"610","author":"ME Morrey","year":"2017","unstructured":"Morrey ME, Abdel MP, Riester SM, Dudakovic A, van Wijnen AJ, Morrey BF et al (2017) Molecular landscape of arthrofibrosis: microarray and bioinformatic analysis of the temporal expression of 380 genes during contracture genesis. Gene 610:15\u201323","journal-title":"Gene"},{"issue":"4","key":"2593_CR35","doi-asserted-by":"publisher","first-page":"588","DOI":"10.1093\/rheumatology\/key186","volume":"58","author":"KR Christensen","year":"2019","unstructured":"Christensen KR, Kjelgaard-Hansen M, Nielsen LN, Wiinberg B, Alexander Althoehn F, Bloksgaard Poulsen N et al (2019) Rapid inflammation and early degeneration of bone and cartilage revealed in a time-course study of induced haemarthrosis in haemophilic rats. Rheumatology (Oxford) 58(4):588\u2013599","journal-title":"Rheumatology (Oxford)"},{"issue":"1","key":"2593_CR36","doi-asserted-by":"publisher","first-page":"119","DOI":"10.1111\/j.1365-2516.2007.01527.x","volume":"14","author":"C Mejia-Carvajal","year":"2008","unstructured":"Mejia-Carvajal C, Hakobyan N, Enockson C, Valentino LA (2008) The impact of joint bleeding and synovitis on physical ability and joint function in a murine model of haemophilic synovitis. Haemophilia 14(1):119\u2013126","journal-title":"Haemophilia"},{"issue":"11","key":"2593_CR37","doi-asserted-by":"publisher","first-page":"1302","DOI":"10.1016\/j.joca.2012.07.021","volume":"20","author":"P Sward","year":"2012","unstructured":"Sward P, Frobell R, Englund M, Roos H, Struglics A (2012) Cartilage and bone markers and inflammatory cytokines are increased in synovial fluid in the acute phase of knee injury (hemarthrosis)\u2013a cross-sectional analysis. Osteoarthritis Cartilage 20(11):1302\u20131308","journal-title":"Osteoarthritis Cartilage"},{"key":"2593_CR38","doi-asserted-by":"publisher","DOI":"10.1038\/s41390-024-03562-0","author":"KL Ding","year":"2024","unstructured":"Ding KL, Smith C, Seedorf G, Abman SH (2024) Nintedanib preserves lung growth and prevents pulmonary hypertension in a hyperoxia-induced lung injury model. Pediatr Res. https:\/\/doi.org\/10.1038\/s41390-024-03562-0","journal-title":"Pediatr Res"},{"issue":"9","key":"2593_CR39","doi-asserted-by":"publisher","first-page":"754","DOI":"10.1136\/thoraxjnl-2019-214000","volume":"75","author":"C Overed-Sayer","year":"2020","unstructured":"Overed-Sayer C, Miranda E, Dunmore R, Liarte Marin E, Beloki L, Rassl D et al (2020) Inhibition of mast cells: a novel mechanism by which nintedanib may elicit anti-fibrotic effects. Thorax 75(9):754\u2013763","journal-title":"Thorax"},{"issue":"7","key":"2593_CR40","doi-asserted-by":"publisher","first-page":"393","DOI":"10.1016\/j.purol.2023.02.010","volume":"33","author":"M Bozkurt","year":"2023","unstructured":"Bozkurt M, Polat EC, Ozcan L, Ozer M, Ozturk GY, Yildirim F et al (2023) Effect of nintedanib on healing and fibrosis in rats with experimentally induced urethral injury. Prog Urol 33(7):393\u2013400","journal-title":"Prog Urol"},{"issue":"11 Suppl A","key":"2593_CR41","doi-asserted-by":"publisher","first-page":"112","DOI":"10.1302\/0301-620X.94B11.30512","volume":"94","author":"EP Su","year":"2012","unstructured":"Su EP (2012) Fixed flexion deformity and total knee arthroplasty. J Bone Joint Surg Br 94(11 Suppl A):112\u2013115","journal-title":"J Bone Joint Surg Br"},{"issue":"5","key":"2593_CR42","doi-asserted-by":"publisher","first-page":"H1871","DOI":"10.1152\/ajpheart.00387.2003","volume":"285","author":"J Wang","year":"2003","unstructured":"Wang J, Chen H, Seth A, McCulloch CA (2003) Mechanical force regulation of myofibroblast differentiation in cardiac fibroblasts. Am J Physiol Heart Circ Physiol 285(5):H1871\u2013H1881","journal-title":"Am J Physiol Heart Circ Physiol"},{"issue":"1","key":"2593_CR43","doi-asserted-by":"publisher","first-page":"298","DOI":"10.1016\/j.bbadis.2016.11.006","volume":"1863","author":"AV Shinde","year":"2017","unstructured":"Shinde AV, Humeres C, Frangogiannis NG (2017) The role of alpha-smooth muscle actin in fibroblast-mediated matrix contraction and remodeling. Biochim Biophys Acta Mol Basis Dis 1863(1):298\u2013309","journal-title":"Biochim Biophys Acta Mol Basis Dis"},{"key":"2593_CR44","doi-asserted-by":"publisher","DOI":"10.1016\/j.pupt.2020.101938","volume":"63","author":"MW Surber","year":"2020","unstructured":"Surber MW, Beck S, Pham S, Marsden AT, Gandi SK, Baily J et al (2020) Inhaled nintedanib is well-tolerated and delivers key pharmacokinetic parameters required to treat bleomycin-induced pulmonary fibrosis. Pulm Pharmacol Ther 63:101938","journal-title":"Pulm Pharmacol Ther"},{"issue":"1","key":"2593_CR45","doi-asserted-by":"publisher","first-page":"44","DOI":"10.1213\/ANE.0000000000001683","volume":"124","author":"K Miotto","year":"2017","unstructured":"Miotto K, Cho AK, Khalil MA, Blanco K, Sasaki JD, Rawson R (2017) Trends in tramadol: pharmacology, metabolism, and misuse. Anesth Analg 124(1):44\u201351","journal-title":"Anesth Analg"},{"key":"2593_CR46","doi-asserted-by":"publisher","first-page":"173","DOI":"10.1016\/j.jpba.2015.08.024","volume":"117","author":"D Lin","year":"2016","unstructured":"Lin D, Qiao LM, Zhang YN, Liu Y, Liu XS (2016) Simultaneous determination of nintedanib and its metabolite by UPLC-MS\/MS in rat plasma and its application to a pharmacokinetic study. J Pharm Biomed Anal 117:173\u2013177","journal-title":"J Pharm Biomed Anal"},{"issue":"4","key":"2593_CR47","doi-asserted-by":"publisher","first-page":"265","DOI":"10.1080\/03008207.2024.2358351","volume":"65","author":"L Palacios-Diaz","year":"2024","unstructured":"Palacios-Diaz L, Gonzalez-Garcia AA, Sanchez Urgelles P, Antuna S, Barco R (2024) Biomechanical outcomes of pharmacological therapies for post-traumatic arthrofibrosis in preclinical animal models: a systematic review and meta-analysis. Connect Tissue Res 65(4):265\u2013278","journal-title":"Connect Tissue Res"}],"container-title":["Journal of Molecular Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00109-025-02593-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00109-025-02593-2\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00109-025-02593-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,3]],"date-time":"2025-12-03T08:02:35Z","timestamp":1764748955000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00109-025-02593-2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9,25]]},"references-count":47,"journal-issue":{"issue":"11-12","published-print":{"date-parts":[[2025,11]]}},"alternative-id":["2593"],"URL":"https:\/\/doi.org\/10.1007\/s00109-025-02593-2","relation":{},"ISSN":["0946-2716","1432-1440"],"issn-type":[{"value":"0946-2716","type":"print"},{"value":"1432-1440","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,9,25]]},"assertion":[{"value":"16 April 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"21 August 2025","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"29 August 2025","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"25 September 2025","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The study was conducted according to the German \u201cLegal ordinance on the Protection of Animals Used for Experimental Purposes or for Other Scientific Purposes (Experimental Animal Welfare Regulation\u2014TierSchVersV),\u201d and was approved by the Ethics Committee of the \u201cLandesuntersuchungsamt Rheinland-Pfalz\u201d (protocol code ID 23 177\u201307\/G 21\u20131-113). The approval was granted on April 19, 2022.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval"}},{"value":"All authors have consented to the publication of this work, and all individuals who provided content have given their consent for publication.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}