{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,12]],"date-time":"2026-06-12T06:55:36Z","timestamp":1781247336591,"version":"3.54.1"},"reference-count":38,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,4,14]],"date-time":"2025-04-14T00:00:00Z","timestamp":1744588800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,4,14]],"date-time":"2025-04-14T00:00:00Z","timestamp":1744588800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100009666","name":"Salt Science Research Foundation","doi-asserted-by":"publisher","award":["22C1"],"award-info":[{"award-number":["22C1"]}],"id":[{"id":"10.13039\/100009666","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001700","name":"Ministry of Education, Culture, Sports, Science, and Technology of Japan","doi-asserted-by":"crossref","award":["23K08642"],"award-info":[{"award-number":["23K08642"]}],"id":[{"id":"10.13039\/501100001700","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Calcif Tissue Int"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Hyponatremia is associated with sarcopenia and osteoporosis in elderly individuals. Skeletal muscle releases myokines, which affect distant organs, including bone. However, the detailed mechanisms by which hyponatremia influences muscle and bone remain unclear. We herein investigated the effects of hyponatremia on muscle, bone, and myokines linking muscle to bone in mice treated with 1-desamino-8-D-arginine vasopressin (dDAVP) or furosemide, which induce hyponatremia. Muscle mass and bone mineral density (BMD) were analyzed 8\u00a0weeks after the administration of dDAVP or furosemide. dDAVP significantly reduced grip strength, but did not affect tissue weights of gastrocnemius or soleus muscles of mice. Furosemide significantly decreased muscle mass, tissue weights of gastrocnemius and soleus muscles, and grip strength in mice. dDAVP and furosemide decreased trabecular BMD, trabecular bone volume, and cortical BMD at the femurs. Among myokines linking muscle to bone, hyponatremia reduced expression of insulin-like growth factor (IGF)-1 in gastrocnemius and soleus muscles and serum IGF-1 levels in mice. In simple regression analyses, serum IGF-1 levels were positively related to muscle IGF-1 expression, trabecular bone volume, and cortical BMD in mice. The administration of sodium chloride solution to mice ameliorated the decreases in grip strength, muscle mass, trabecular bone volume, cortical BMD, and the levels of muscle and circulating IGF-1 in furosemide-treated mice. The present study demonstrated that hyponatremia induces muscle and bone loss as well as a decrease in muscle IGF-1 expression in mice. The present findings suggest that IGF-1 might be related to muscle wasting and bone loss induced by hyponatremia in mice.<\/jats:p>","DOI":"10.1007\/s00223-025-01369-7","type":"journal-article","created":{"date-parts":[[2025,4,14]],"date-time":"2025-04-14T01:06:06Z","timestamp":1744592766000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Roles of Insulin-Like Growth Factor-1 in Muscle Wasting and Osteopenia in Mice with Hyponatremia"],"prefix":"10.1007","volume":"116","author":[{"given":"Naoyuki","family":"Kawao","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akihito","family":"Nishikawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daichi","family":"Matsumura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ayaka","family":"Yamada","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takashi","family":"Ohira","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuya","family":"Mizukami","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7433-5135","authenticated-orcid":false,"given":"Hiroshi","family":"Kaji","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,4,14]]},"reference":[{"key":"1369_CR1","doi-asserted-by":"publisher","first-page":"S1","DOI":"10.1016\/j.amjmed.2013.07.006","volume":"126","author":"JG Verbalis","year":"2013","unstructured":"Verbalis JG, Goldsmith SR, Greenberg A, Korzelius C, Schrier RW, Sterns RH, Thompson CJ (2013) Diagnosis, evaluation, and treatment of hyponatremia: expert panel recommendations. Am J Med 126:S1-42","journal-title":"Am J Med"},{"key":"1369_CR2","doi-asserted-by":"publisher","first-page":"554","DOI":"10.1359\/jbmr.090827","volume":"25","author":"JG Verbalis","year":"2010","unstructured":"Verbalis JG, Barsony J, Sugimura Y, Tian Y, Adams DJ, Carter EA, Resnick HE (2010) Hyponatremia-induced osteoporosis. J Bone Miner Res 25:554\u2013563","journal-title":"J Bone Miner Res"},{"key":"1369_CR3","doi-asserted-by":"publisher","first-page":"10864","DOI":"10.1074\/jbc.M110.155002","volume":"286","author":"J Barsony","year":"2011","unstructured":"Barsony J, Sugimura Y, Verbalis JG (2011) Osteoclast response to low extracellular sodium and the mechanism of hyponatremia-induced bone loss. J Biol Chem 286:10864\u201310875","journal-title":"J Biol Chem"},{"key":"1369_CR4","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbc.2023.105480","volume":"300","author":"Z Radvanyi","year":"2024","unstructured":"Radvanyi Z, Yoo EJ, Kandasamy P, Salas-Bastos A, Monnerat S, Refardt J, Christ-Crain M, Hayashi H, Kondo Y, Jantsch J, Rubio-Aliaga I, Sommer L, Wagner CA, Hediger MA, Kwon HM, Loffing J, Pathare G (2024) Extracellular sodium regulates fibroblast growth factor 23 (FGF23) formation. J Biol Chem 300:105480","journal-title":"J Biol Chem"},{"key":"1369_CR5","doi-asserted-by":"publisher","first-page":"1822","DOI":"10.1002\/jbmr.380","volume":"26","author":"EJ Hoorn","year":"2011","unstructured":"Hoorn EJ, Rivadeneira F, van Meurs JB, Ziere G, Stricker BH, Hofman A, Pols HA, Zietse R, Uitterlinden AG, Zillikens MC (2011) Mild hyponatremia as a risk factor for fractures: the Rotterdam Study. J Bone Miner Res 26:1822\u20131828","journal-title":"J Bone Miner Res"},{"key":"1369_CR6","doi-asserted-by":"publisher","first-page":"970","DOI":"10.1002\/jbmr.2383","volume":"30","author":"SA Jamal","year":"2015","unstructured":"Jamal SA, Arampatzis S, Harrison SL, Bucur RC, Ensrud K, Orwoll ES, Bauer DC (2015) Hyponatremia and fractures: findings from the MrOS study. J Bone Miner Res 30:970\u2013975","journal-title":"J Bone Miner Res"},{"key":"1369_CR7","doi-asserted-by":"publisher","first-page":"3021","DOI":"10.1210\/jc.2015-1261","volume":"100","author":"RL Usala","year":"2015","unstructured":"Usala RL, Fernandez SJ, Mete M, Cowen L, Shara NM, Barsony J, Verbalis JG (2015) Hyponatremia is associated with increased osteoporosis and bone fractures in a large US health system population. J Clin Endocrinol Metab 100:3021\u20133031","journal-title":"J Clin Endocrinol Metab"},{"key":"1369_CR8","doi-asserted-by":"publisher","first-page":"1880","DOI":"10.1210\/jc.2015-4228","volume":"101","author":"S Upala","year":"2016","unstructured":"Upala S, Sanguankeo A (2016) Association between hyponatremia, osteoporosis, and fracture: a systematic review and meta-analysis. J Clin Endocrinol Metab 101:1880\u20131886","journal-title":"J Clin Endocrinol Metab"},{"key":"1369_CR9","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1159\/000493237","volume":"52","author":"J Barsony","year":"2019","unstructured":"Barsony J, Kleess L, Verbalis JG (2019) Hyponatremia is linked to bone loss, osteoporosis, fragility and bone fractures. Front Horm Res 52:49\u201360","journal-title":"Front Horm Res"},{"key":"1369_CR10","doi-asserted-by":"publisher","first-page":"271","DOI":"10.1007\/s11357-011-9347-9","volume":"35","author":"J Barsony","year":"2013","unstructured":"Barsony J, Manigrasso MB, Xu Q, Tam H, Verbalis JG (2013) Chronic hyponatremia exacerbates multiple manifestations of senescence in male rats. Age (Dordr) 35:271\u2013288","journal-title":"Age (Dordr)"},{"key":"1369_CR11","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1186\/s12877-020-01955-4","volume":"21","author":"C Fujisawa","year":"2021","unstructured":"Fujisawa C, Umegaki H, Sugimoto T, Samizo S, Huang CH, Fujisawa H, Sugimura Y, Kuzuya M, Toba K, Sakurai T (2021) Mild hyponatremia is associated with low skeletal muscle mass, physical function impairment, and depressive mood in the elderly. BMC Geriatr 21:15","journal-title":"BMC Geriatr"},{"key":"1369_CR12","doi-asserted-by":"publisher","DOI":"10.3389\/fmed.2020.610659","volume":"7","author":"A Markaki","year":"2020","unstructured":"Markaki A, Kyriazis P, Dermitzaki EK, Maragou S, Psylinakis E, Spyridaki A, Drosataki H, Lygerou D, Grammatikopoulou MG, Petrakis I, Stylianou K (2020) The association between handgrip strength and predialysis serum sodium level in patients with chronic kidney disease stage 5D. Front Med (Lausanne) 7:610659","journal-title":"Front Med (Lausanne)"},{"key":"1369_CR13","doi-asserted-by":"publisher","first-page":"687","DOI":"10.1002\/jcb.25040","volume":"116","author":"N Kawao","year":"2015","unstructured":"Kawao N, Kaji H (2015) Interactions between muscle tissues and bone metabolism. J Cell Biochem 116:687\u2013695","journal-title":"J Cell Biochem"},{"key":"1369_CR14","doi-asserted-by":"publisher","first-page":"2547","DOI":"10.3390\/ijms21072547","volume":"21","author":"N Kawao","year":"2020","unstructured":"Kawao N, Morita H, Iemura S, Ishida M, Kaji H (2020) Roles of Dkk2 in the linkage from muscle to bone during mechanical unloading in mice. Int J Mol Sci 21:2547","journal-title":"Int J Mol Sci"},{"key":"1369_CR15","doi-asserted-by":"publisher","first-page":"180","DOI":"10.1007\/s00223-020-00710-6","volume":"107","author":"T Shimoide","year":"2020","unstructured":"Shimoide T, Kawao N, Morita H, Ishida M, Takafuji Y, Kaji H (2020) Roles of olfactomedin 1 in muscle and bone alterations induced by gravity change in mice. Calcif Tissue Int 107:180\u2013190","journal-title":"Calcif Tissue Int"},{"key":"1369_CR16","doi-asserted-by":"publisher","first-page":"1191","DOI":"10.1002\/jcp.25986","volume":"233","author":"N Kawao","year":"2018","unstructured":"Kawao N, Morita H, Obata K, Tatsumi K, Kaji H (2018) Role of follistatin in muscle and bone alterations induced by gravity change in mice. J Cell Physiol 233:1191\u20131201","journal-title":"J Cell Physiol"},{"key":"1369_CR17","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1007\/s00223-018-0387-3","volume":"103","author":"N Kawao","year":"2018","unstructured":"Kawao N, Moritake A, Tatsumi K, Kaji H (2018) Roles of irisin in the linkage from muscle to bone during mechanical unloading in mice. Calcif Tissue Int 103:24\u201334","journal-title":"Calcif Tissue Int"},{"key":"1369_CR18","doi-asserted-by":"publisher","first-page":"547","DOI":"10.1007\/s00774-020-01201-2","volume":"39","author":"N Kawao","year":"2021","unstructured":"Kawao N, Iemura S, Kawaguchi M, Mizukami Y, Takafuji Y, Kaji H (2021) Role of irisin in effects of chronic exercise on muscle and bone in ovariectomized mice. J Bone Miner Metab 39:547\u2013557","journal-title":"J Bone Miner Metab"},{"key":"1369_CR19","doi-asserted-by":"publisher","first-page":"758","DOI":"10.1002\/jcsm.12892","volume":"13","author":"N Kawao","year":"2022","unstructured":"Kawao N, Kawaguchi M, Ohira T, Ehara H, Mizukami Y, Takafuji Y, Kaji H (2022) Renal failure suppresses muscle irisin expression, and irisin blunts cortical bone loss in mice. J Cachexia Sarcopenia Muscle 13:758\u2013771","journal-title":"J Cachexia Sarcopenia Muscle"},{"key":"1369_CR20","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1507\/endocrj.EJ20-0289","volume":"68","author":"T Kawakami","year":"2021","unstructured":"Kawakami T, Fujisawa H, Nakayama S, Yoshino Y, Hattori S, Seino Y, Takayanagi T, Miyakawa T, Suzuki A, Sugimura Y (2021) Vasopressin escape and memory impairment in a model of chronic syndrome of inappropriate secretion of antidiuretic hormone in mice. Endocr J 68:31\u201343","journal-title":"Endocr J"},{"key":"1369_CR21","doi-asserted-by":"publisher","first-page":"128","DOI":"10.1016\/j.kint.2017.06.008","volume":"93","author":"JW Lee","year":"2018","unstructured":"Lee JW, Alsady M, Chou CL, de Groot T, Deen PMT, Knepper MA, Ecelbarger CM (2018) Single-tubule RNA-Seq uncovers signaling mechanisms that defend against hyponatremia in SIADH. Kidney Int 93:128\u2013146","journal-title":"Kidney Int"},{"key":"1369_CR22","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2024.117040","volume":"181","author":"N Kawao","year":"2024","unstructured":"Kawao N, Matsumura D, Yamada A, Okumoto K, Ohira T, Mizukami Y, Hashimoto D, Kaji H (2024) Tmem119 is involved in bone anabolic effects of PTH through enhanced osteoblastic bone formation in mice. Bone 181:117040","journal-title":"Bone"},{"key":"1369_CR23","doi-asserted-by":"publisher","first-page":"1468","DOI":"10.1002\/jbmr.141","volume":"25","author":"ML Bouxsein","year":"2010","unstructured":"Bouxsein ML, Boyd SK, Christiansen BA, Guldberg RE, Jepsen KJ, Muller R (2010) Guidelines for assessment of bone microstructure in rodents using micro-computed tomography. J Bone Miner Res 25:1468\u20131486","journal-title":"J Bone Miner Res"},{"key":"1369_CR24","doi-asserted-by":"publisher","first-page":"826","DOI":"10.1038\/bonekey.2016.48","volume":"5","author":"H Kaji","year":"2016","unstructured":"Kaji H (2016) Effects of myokines on bone. Bonekey Rep 5:826","journal-title":"Bonekey Rep"},{"key":"1369_CR25","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1016\/j.bone.2015.04.036","volume":"80","author":"DD Bikle","year":"2015","unstructured":"Bikle DD, Tahimic C, Chang W, Wang Y, Philippou A, Barton ER (2015) Role of IGF-I signaling in muscle bone interactions. Bone 80:79\u201388","journal-title":"Bone"},{"key":"1369_CR26","doi-asserted-by":"publisher","first-page":"1773","DOI":"10.3390\/cells9081773","volume":"9","author":"SS Ahmad","year":"2020","unstructured":"Ahmad SS, Ahmad K, Lee EJ, Lee YH, Choi I (2020) Implications of insulin-like growth factor-1 in skeletal muscle and various diseases. Cells 9:1773","journal-title":"Cells"},{"key":"1369_CR27","doi-asserted-by":"publisher","DOI":"10.1155\/2012\/127362","volume":"2012","author":"K Sakuma","year":"2012","unstructured":"Sakuma K, Yamaguchi A (2012) Sarcopenia and age-related endocrine function. Int J Endocrinol 2012:127362","journal-title":"Int J Endocrinol"},{"key":"1369_CR28","doi-asserted-by":"publisher","first-page":"1271","DOI":"10.1359\/jbmr.070506","volume":"22","author":"JJ Cao","year":"2007","unstructured":"Cao JJ, Kurimoto P, Boudignon B, Rosen C, Lima F, Halloran BP (2007) Aging impairs IGF-I receptor activation and induces skeletal resistance to IGF-I. J Bone Miner Res 22:1271\u20131279","journal-title":"J Bone Miner Res"},{"key":"1369_CR29","doi-asserted-by":"publisher","first-page":"1287972","DOI":"10.3389\/fendo.2023.1287972","volume":"14","author":"Z Zhao","year":"2023","unstructured":"Zhao Z, Yan K, Guan Q, Guo Q, Zhao C (2023) Mechanism and physical activities in bone-skeletal muscle crosstalk. Front Endocrinol (Lausanne) 14:1287972","journal-title":"Front Endocrinol (Lausanne)"},{"key":"1369_CR30","doi-asserted-by":"publisher","first-page":"1683","DOI":"10.3390\/nu12061683","volume":"12","author":"TH Chiu","year":"2020","unstructured":"Chiu TH, Chen SC, Yu HC, Hsu JS, Shih MC, Jiang HJ, Hsu WH, Lee MY (2020) Association between geriatric nutrition risk index and skeletal muscle mass index with bone mineral density in post-menopausal women who have undergone total thyroidectomy. Nutrients 12:1683","journal-title":"Nutrients"},{"key":"1369_CR31","doi-asserted-by":"publisher","DOI":"10.1002\/jcsm.13484","author":"L Ma","year":"2024","unstructured":"Ma L, Meng Y, An Y, Han P, Zhang C, Yue Y, Wen C, Shi X, Jin J, Yang G, Li X (2024) Single-cell RNA-seq reveals novel interaction between muscle satellite cells and fibro-adipogenic progenitors mediated with FGF7 signalling. J Cachexia Sarcopenia Muscle. https:\/\/doi.org\/10.1002\/jcsm.13484","journal-title":"J Cachexia Sarcopenia Muscle"},{"issue":"2029\u20132035","key":"1369_CR32","volume":"27","author":"MN Wosczyna","year":"2019","unstructured":"Wosczyna MN, Konishi CT, Perez Carbajal EE, Wang TT, Walsh RA, Gan Q, Wagner MW, Rando TA (2019) Mesenchymal stromal cells are required for regeneration and homeostatic maintenance of skeletal muscle. Cell Rep 27(2029\u20132035):e2025","journal-title":"Cell Rep"},{"key":"1369_CR33","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1530\/EJE-18-0076","volume":"179","author":"IC van Nieuwpoort","year":"2018","unstructured":"van Nieuwpoort IC, Vlot MC, Schaap LA, Lips P, Drent ML (2018) The relationship between serum IGF-1, handgrip strength, physical performance and falls in elderly men and women. Eur J Endocrinol 179:73\u201384","journal-title":"Eur J Endocrinol"},{"key":"1369_CR34","doi-asserted-by":"publisher","first-page":"621","DOI":"10.1089\/scd.2005.14.621","volume":"14","author":"H Koch","year":"2005","unstructured":"Koch H, Jadlowiec JA, Campbell PG (2005) Insulin-like growth factor-I induces early osteoblast gene expression in human mesenchymal stem cells. Stem Cells Dev 14:621\u2013631","journal-title":"Stem Cells Dev"},{"key":"1369_CR35","doi-asserted-by":"publisher","first-page":"771","DOI":"10.1172\/JCI0215463","volume":"110","author":"S Yakar","year":"2002","unstructured":"Yakar S, Rosen CJ, Beamer WG, Ackert-Bicknell CL, Wu Y, Liu JL, Ooi GT, Setser J, Frystyk J, Boisclair YR, LeRoith D (2002) Circulating levels of IGF-1 directly regulate bone growth and density. J Clin Invest 110:771\u2013781","journal-title":"J Clin Invest"},{"key":"1369_CR36","doi-asserted-by":"publisher","first-page":"1977","DOI":"10.1359\/jbmr.2002.17.11.1977","volume":"17","author":"K Sjogren","year":"2002","unstructured":"Sjogren K, Sheng M, Moverare S, Liu JL, Wallenius K, Tornell J, Isaksson O, Jansson JO, Mohan S, Ohlsson C (2002) Effects of liver-derived insulin-like growth factor I on bone metabolism in mice. J Bone Miner Res 17:1977\u20131987","journal-title":"J Bone Miner Res"},{"key":"1369_CR37","doi-asserted-by":"publisher","first-page":"3691","DOI":"10.1096\/fj.11-203026","volume":"26","author":"ER Barton","year":"2012","unstructured":"Barton ER, Park S, James JK, Makarewich CA, Philippou A, Eletto D, Lei H, Brisson B, Ostrovsky O, Li Z, Argon Y (2012) Deletion of muscle GRP94 impairs both muscle and body growth by inhibiting local IGF production. FASEB J 26:3691\u20133702","journal-title":"FASEB J"},{"key":"1369_CR38","doi-asserted-by":"publisher","first-page":"221","DOI":"10.1096\/fj.03-0293fje","volume":"18","author":"MB Alzghoul","year":"2004","unstructured":"Alzghoul MB, Gerrard D, Watkins BA, Hannon K (2004) Ectopic expression of IGF-I and Shh by skeletal muscle inhibits disuse-mediated skeletal muscle atrophy and bone osteopenia in vivo. FASEB J 18:221\u2013223","journal-title":"FASEB J"}],"container-title":["Calcified Tissue International"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00223-025-01369-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00223-025-01369-7","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00223-025-01369-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,26]],"date-time":"2025-12-26T13:21:34Z","timestamp":1766755294000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00223-025-01369-7"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,4,14]]},"references-count":38,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["1369"],"URL":"https:\/\/doi.org\/10.1007\/s00223-025-01369-7","relation":{},"ISSN":["1432-0827"],"issn-type":[{"value":"1432-0827","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,4,14]]},"assertion":[{"value":"9 October 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"2 April 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"14 April 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors Naoyuki Kawao, AkihitoNishikawa, Daichi Matsumura, AyakaYamada, Takashi Ohira, Yuya Mizukami and Hiroshi Kaji declare that they have no conflict of interest.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}},{"value":"Animal experiments were performed in accordance with the guidelines of ARRIVE and the institutional rules for the use and care of laboratory animals at Kindai University. All experimental procedures on animals were approved by the Experimental Animal Welfare Committee of Kindai University (Permit number: KAME-2022-079).","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical Approval"}},{"value":"All applicable international, national, and\/or institutional guidelines for the care and use of animals were followed. All procedures performed in studies involving animals were in accordance with the ethical standards of the institution or practice at which the studies were conducted. This study does not contain any studies with human participants performed by any of the authors.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Research Involving Human and Animal Participants and Informed Consent"}}],"article-number":"61"}}