{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T01:03:28Z","timestamp":1787792608134,"version":"build-2784847793"},"reference-count":29,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2023,6,17]],"date-time":"2023-06-17T00:00:00Z","timestamp":1686960000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["2021R1C1C1008734"],"award-info":[{"award-number":["2021R1C1C1008734"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["2018R1A6A3A11050852"],"award-info":[{"award-number":["2018R1A6A3A11050852"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["2022R1A2B5B02001671"],"award-info":[{"award-number":["2022R1A2B5B02001671"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Andrology"],"published-print":{"date-parts":[[2024,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>The odds of erectile dysfunction are three times more prevalent in diabetes. Severe peripheral vascular and neural damage in diabetic patients responds poorly to phosphodiesterase\u20105 (PDE5) inhibitors. However, bone morphogenetic protein 2 is known to be involved in angiogenesis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>To assess the efficacy of bone morphogenetic protein 2 in stimulating angiogenesis and augmenting nerve regeneration in a mouse model of diabetic\u2010induced erectile dysfunction.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and methods<\/jats:title>\n                    <jats:p>The induction of diabetes mellitus was performed by streptozotocin (50\u00a0mg\/kg daily) administered intraperitoneally for 5 successive days to male C57BL\/6 mice that were 8\u00a0weeks old. Eight weeks post\u2010inductions, animals were allocated to one of five groups: a control group, a streptozotocin\u2010induced diabetic mouse group receiving two intracavernous 20\u00a0\u03bcL phosphate\u2010buffered saline injections, or one of three bone morphogenetic protein 2 groups administered two injections of bone morphogenetic protein 2 protein (1, 5, or 10\u00a0\u03bcg) diluted in 20\u00a0\u03bcL of phosphate\u2010buffered saline within a 3\u2010day interval between the first and second injections. The erectile functions were assessed 2 weeks after phosphate\u2010buffered saline or bone morphogenetic protein 2 protein injections by recording the intracavernous pressure through cavernous nerve electrical stimulation. Angiogenic activities and nerve regenerating effects of bone morphogenetic protein 2 were determined in penile tissues, aorta, vena cava, the main pelvic ganglions, the dorsal roots, and from the primary cultured mouse cavernous endothelial cells. Moreover, fibrosis\u2010related factor protein expressions were evaluated by western blotting.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Erectile function recovery to 81% of the control value in diabetic mice was found with intracavernous bone morphogenetic protein 2 injection (5\u00a0\u03bcg\/20\u00a0\u03bcL). Pericytes and endothelial cells were extensively restored. It was confirmed that angiogenesis was promoted in the corpus cavernosum of diabetic mice treated with bone morphogenetic protein 2 through increased ex vivo sprouting of aortic rings, vena cava and penile tissues, and migration and tube formation of mouse cavernous endothelial cells. Bone morphogenetic protein 2 protein enhanced cell proliferation and reduced apoptosis in mouse cavernous endothelial cells and penile tissues, and promoted neurite outgrowth in major pelvic ganglia and dorsal root ganglia under high\u2010glucose conditions. Furthermore, bone morphogenetic protein 2 suppressed fibrosis by reducing mouse cavernous endothelial cell fibronectin, collagen 1, and collagen 4 levels under high\u2010glucose conditions.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Bone morphogenetic protein 2 modulates neurovascular regeneration and inhibits fibrosis to revive the mouse erection function in diabetic conditions. Our findings propose that the bone morphogenetic protein 2 protein represents a novel and promising approach to treating diabetes\u2010related erectile dysfunction.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/andr.13475","type":"journal-article","created":{"date-parts":[[2023,6,8]],"date-time":"2023-06-08T18:09:36Z","timestamp":1686247776000},"page":"447-458","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["BMP2 restores erectile dysfunction through neurovascular regeneration and fibrosis reduction in diabetic mice"],"prefix":"10.1111","volume":"12","author":[{"given":"Mi\u2010Hye","family":"Kwon","sequence":"first","affiliation":[{"name":"National Research Center for Sexual Medicine and Department of Urology Inha University College of Medicine Incheon Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beom Yong","family":"Rho","sequence":"additional","affiliation":[{"name":"National Research Center for Sexual Medicine and Department of Urology Inha University College of Medicine Incheon Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min\u2010Ji","family":"Choi","sequence":"additional","affiliation":[{"name":"National Research Center for Sexual Medicine and Department of Urology Inha University College of Medicine Incheon Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anita","family":"Limanjaya","sequence":"additional","affiliation":[{"name":"National Research Center for Sexual Medicine and Department of Urology Inha University College of Medicine Incheon Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiyeon","family":"Ock","sequence":"additional","affiliation":[{"name":"National Research Center for Sexual Medicine and Department of Urology Inha University College of Medicine Incheon Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guo Nan","family":"Yin","sequence":"additional","affiliation":[{"name":"National Research Center for Sexual Medicine and Department of Urology Inha University College of Medicine Incheon Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suk\u2010Won","family":"Jin","sequence":"additional","affiliation":[{"name":"School of Life Sciences and Cell Logistics Research Center Gwangju Institute of Science and Technology Gwangju Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun\u2010Kyu","family":"Suh","sequence":"additional","affiliation":[{"name":"National Research Center for Sexual Medicine and Department of Urology Inha University College of Medicine Incheon Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Doo Yong","family":"Chung","sequence":"additional","affiliation":[{"name":"National Research Center for Sexual Medicine and Department of Urology Inha University College of Medicine Incheon Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2512-7337","authenticated-orcid":false,"given":"Ji\u2010Kan","family":"Ryu","sequence":"additional","affiliation":[{"name":"National Research Center for Sexual Medicine and Department of Urology Inha University College of Medicine Incheon Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,6,17]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ucl.2005.08.007"},{"key":"e_1_2_9_3_1","doi-asserted-by":"crossref","unstructured":"NIH Consensus Conference. 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