{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T13:29:41Z","timestamp":1781616581644,"version":"3.54.5"},"reference-count":33,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,11,1]],"date-time":"2021-11-01T00:00:00Z","timestamp":1635724800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100018610","name":"Innovation Program in Military Medicine of Chinese People\u2019s Liberation Army","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100018610","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell Dev. Biol."],"abstract":"<jats:p>Bone regeneration is a delicate physiological process. Non-union and delayed fracture healing remains a great challenge in clinical practice nowadays. Bone and fat hold a close relationship to remain balanced through hormones and cytokines. Adiponectin is a well-known protein to maintain the hemostasis, which may be an interesting target for fracture healing. Herein, we provided a facile and efficient method to obtain high-purity and high-yield recombinant human adiponectin (ADPN). The biocompatibility and the pharmaceutical behaviors were evaluated in Sprague\u2013Dawley rats. The paracrine effects of adiponectin on bone fracture healing were investigated with a rat tibia fracture model <jats:italic>via<\/jats:italic> intrabone injection. Significantly accelerated bone healing was observed in the medulla injection group, indicating the paracrine effects of adiponectin could be potentially utilized for clinical treatments. The underlying mechanism was primarily assessed, and the expression of osteogenic markers, including bone morphogenic protein 2, alkaline phosphatase, and osteocalcin, along with adiponectin receptor 1 (AdipoR1), was markedly increased at the fracture site. The increased bone healing of ADPN treatment may result from both enhanced osteogenic proliferation as well as differentiation. Cell experiments confirmed that the expression of osteogenesis markers increased significantly in ADPN treatment groups, while it decreased when the expression of AdipoR1 was knocked down by siRNA. Our study provided a feasible and efficacious way for bone fracture treatment with local administration of ADPN, which could be rapidly translated into the clinics.<\/jats:p>","DOI":"10.3389\/fcell.2021.762335","type":"journal-article","created":{"date-parts":[[2021,11,1]],"date-time":"2021-11-01T06:26:36Z","timestamp":1635747996000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":8,"title":["Paracrine Effects of Recombinant Human Adiponectin Promote Bone Regeneration"],"prefix":"10.3389","volume":"9","author":[{"given":"Yanping","family":"Gong","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiqing","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liangchen","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lijuan","family":"Wan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan","family":"Zu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunlin","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhong-Kai","family":"Cui","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,11,1]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"570","DOI":"10.1016\/j.joms.2008.09.023","article-title":"morbidity from anterior iliac crest bone harvesting for secondary alveolar bone grafting: an outcome assessment study.","volume":"67","author":"Baqain","year":"2009","journal-title":"J. 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