{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T23:16:42Z","timestamp":1787613402401,"version":"build-2736575974"},"reference-count":78,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2021,1,18]],"date-time":"2021-01-18T00:00:00Z","timestamp":1610928000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["1R01DK120866\u201001"],"award-info":[{"award-number":["1R01DK120866\u201001"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J cachexia sarcopenia muscle"],"published-print":{"date-parts":[[2021,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Diabetic myopathy involves hyperglycaemia and inflammation that causes skeletal muscle dysfunction; however, the potential cellular mechanisms that occur between hyperglycaemia and inflammation, which induces sarcopenia, and muscle dysfunction remain unknown. In this study, we investigated hyperglycaemia\u2010induced inflammation mediating high\u2010mobility group box 1 activation, which is involved in a novel form of cell death, pyroptosis, diabetic sarcopenia, atrophy, and adverse muscle remodelling. Furthermore, we investigated the therapeutic potential of bone morphogenetic protein\u20107 (BMP\u20107), an osteoporosis drug, to treat pyroptosis, and diabetic muscle myopathy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>C57BL6 mice were treated with saline (control), streptozotocin (STZ), or STZ\u00a0+\u00a0BMP\u20107 to generate diabetic muscle myopathy. Diabetes was established by determining the increased levels of glucose. Then, muscle function was examined, and animals were sacrificed. Gastrocnemius muscle or blood samples were analysed for inflammation, pyroptosis, weight loss, muscle atrophy, and adverse structural remodelling of gastrocnemius muscle using histology, enzyme\u2010linked immunosorbent assay, immunohistochemistry, western blotting, and reverse transcription polymerase chain reaction.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      A significant (\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0&lt;\u00a00.05) increase in hyperglycaemia leads to an increase in inflammasome (high\u2010mobility group box 1, toll\u2010like receptor\u20104, and nucleotide\u2010binding oligomerization domain, leucine\u2010rich repeat and pyrin domain containing protein 3) formation in diabetic muscle cells. Further analysis showed an up\u2010regulation of the downstream pyroptotic pathway with significant (\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0&lt;\u00a00.05) number of positive muscle cells expressing pyroptosis\u2010specific markers [caspase\u20101, interleukin (IL)\u20101\u03b2, IL\u201018, and gasdermin\u2010D]. Pyroptotic cell death is involved in further increasing inflammation by releasing pro\u2010inflammatory cytokine IL\u20106. Structural analysis showed the loss of muscle weight, decreased myofibrillar area, and increased fibrosis leading to muscle dysfunction. Consistent with this finding, BMP\u20107 attenuated hyperglycaemia (~50%), pyroptosis, inflammation, and diabetic adverse structural modifications as well as improved muscle function.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>In conclusion, we report for the first time that increased hyperglycaemia and inflammation involve cellular pyroptosis that induces significant muscle cell loss and adverse remodelling in diabetic myopathy. We also report that targeting pyroptosis with BMP\u20107 improves diabetic muscle pathophysiology and muscle function. These findings suggest that BMP\u20107 could be a potential therapeutic option to treat diabetic myopathy.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/jcsm.12662","type":"journal-article","created":{"date-parts":[[2021,1,19]],"date-time":"2021-01-19T01:40:32Z","timestamp":1611020432000},"page":"403-420","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":100,"title":["Amelioration of diabetes\u2010induced inflammation mediated pyroptosis, sarcopenia, and adverse muscle remodelling by bone morphogenetic protein\u20107"],"prefix":"10.1002","volume":"12","author":[{"given":"Chandrakala","family":"Aluganti Narasimhulu","sequence":"first","affiliation":[{"name":"Division of Metabolic and Cardiovascular Sciences, Burnett School of Biomedical Sciences, College of Medicine University of Central Florida  Orlando FL 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 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,1,18]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc06-2537"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc09-0264"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.53.4.1082"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.2337\/diacare.28.3.745"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc07-zb03"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.2006-0251"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12192-008-0062-0"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.exger.2006.08.011"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-015-3654-0"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1155\/2018\/2063179"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00129.2003"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro2070"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1155\/2017\/9743280"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/imr.12534"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/cr.2015.124"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0903485106"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1097\/SPC.0000000000000013"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00367.2014"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0147897"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0084009"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells8101224"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.3727\/096368914X679200"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.01277.2006"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0075580"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-61737-982-6_5"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0182704"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajpath.2011.07.009"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1242\/dmm.013946"},{"key":"e_1_2_9_30_1","article-title":"Measuring the strength of mice","volume":"2610","author":"Deacon RM","year":"2013","journal-title":"J Vis Exp"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1097\/SHK.0b013e318186262d"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1582-4934.2011.01381.x"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00056.2019"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2017.00519"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10557-013-6501-x"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-065X.2011.01044.x"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.7150\/ijbs.33568"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tibs.2016.10.004"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.00204.2014"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2213-8587(14)70034-8"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1042\/cs0890431"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.1995.1168"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2017.01045"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.3164\/jcbn.11-012FR"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI29069"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0051768"},{"key":"e_1_2_9_47_1","doi-asserted-by":"publisher","DOI":"10.1097\/CCM.0b013e318180b3ba"},{"key":"e_1_2_9_48_1","doi-asserted-by":"publisher","DOI":"10.1177\/0148607194018005398"},{"key":"e_1_2_9_49_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-immunol-030409-101323"},{"key":"e_1_2_9_50_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molimm.2012.10.037"},{"key":"e_1_2_9_51_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.176.12.7154"},{"key":"e_1_2_9_52_1","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.73.4.1907-1916.2005"},{"key":"e_1_2_9_53_1","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.71.8.4382-4388.2003"},{"key":"e_1_2_9_54_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(00)80209-5"},{"key":"e_1_2_9_55_1","doi-asserted-by":"publisher","DOI":"10.1139\/cjpp-2017-0340"},{"key":"e_1_2_9_56_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2017.00351"},{"key":"e_1_2_9_57_1","doi-asserted-by":"publisher","DOI":"10.1536\/ihj.13-388"},{"key":"e_1_2_9_58_1","doi-asserted-by":"publisher","DOI":"10.15252\/emmm.201810248"},{"key":"e_1_2_9_59_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1419090112"},{"key":"e_1_2_9_60_1","doi-asserted-by":"publisher","DOI":"10.1093\/ndt\/gft332"},{"key":"e_1_2_9_61_1","doi-asserted-by":"publisher","DOI":"10.1038\/cr.2015.139"},{"key":"e_1_2_9_62_1","doi-asserted-by":"publisher","DOI":"10.1002\/jnr.24385"},{"key":"e_1_2_9_63_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.285.5425.248"},{"key":"e_1_2_9_64_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3815-05.2006"},{"key":"e_1_2_9_65_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.23602"},{"key":"e_1_2_9_66_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2015.11.003"},{"key":"e_1_2_9_67_1","doi-asserted-by":"publisher","DOI":"10.1159\/000369736"},{"key":"e_1_2_9_68_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep31895"},{"key":"e_1_2_9_69_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.12713"},{"key":"e_1_2_9_70_1","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a016295"},{"key":"e_1_2_9_71_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.autrev.2020.102537"},{"key":"e_1_2_9_72_1","doi-asserted-by":"publisher","DOI":"10.1164\/ajrccm.164.8.2008109"},{"key":"e_1_2_9_73_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI117244"},{"key":"e_1_2_9_74_1","doi-asserted-by":"publisher","DOI":"10.1053\/euhj.1998.1446"},{"key":"e_1_2_9_75_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cytogfr.2011.08.001"},{"key":"e_1_2_9_76_1","doi-asserted-by":"publisher","DOI":"10.1017\/S0029665117001951"},{"key":"e_1_2_9_77_1","doi-asserted-by":"publisher","DOI":"10.2165\/11536910-000000000-00000"},{"key":"e_1_2_9_78_1","doi-asserted-by":"publisher","DOI":"10.1093\/gerona\/gls007"},{"key":"e_1_2_9_79_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2013-2835"}],"container-title":["Journal of Cachexia, Sarcopenia and Muscle"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jcsm.12662","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/jcsm.12662","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jcsm.12662","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,19]],"date-time":"2023-08-19T17:11:09Z","timestamp":1692465069000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jcsm.12662"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,1,18]]},"references-count":78,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2021,4]]}},"alternative-id":["10.1002\/jcsm.12662"],"URL":"https:\/\/doi.org\/10.1002\/jcsm.12662","archive":["Portico"],"relation":{},"ISSN":["2190-5991","2190-6009"],"issn-type":[{"value":"2190-5991","type":"print"},{"value":"2190-6009","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,1,18]]},"assertion":[{"value":"2020-06-18","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-11-23","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-01-18","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}