{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,6]],"date-time":"2026-09-06T18:22:33Z","timestamp":1788718953774,"version":"build-2803163510"},"reference-count":90,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2024,1,31]],"date-time":"2024-01-31T00:00:00Z","timestamp":1706659200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,1,31]],"date-time":"2024-01-31T00:00:00Z","timestamp":1706659200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R03DE028035"],"award-info":[{"award-number":["R03DE028035"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Based on anti-inflammatory and osteogenic properties of hesperidin (HE), we hypothesized its systemic administration could be a cost-effective method of improving BMP-induced bone regeneration. Sprague\u2013Dawley rats were allocated into 4 groups (n\u2009=\u200910\/group): a 5-mm critical-sized mandible defect\u2009+\u2009collagen scaffold or, scaffold +\u20091\u00a0\u00b5g of BMP2 with and without dietary HE at 100\u00a0mg\/kg. HE was administered by oral gavage 4\u00a0weeks prior to surgeries until euthanasia at day 7 or 14\u00a0post-surgery. The healing tissue within the defect collected at day 7 was subjected to gene expression analysis. Mandibles harvested at day 14 were subjected to microcomputed tomography and histology. HE\u2009+\u2009BMP2-treated rats had a statistically significant decrease in expression of inflammatory genes compared to BMP2 alone. The high-dose BMP2 alone\u00a0caused cystic-like regeneration with incomplete defect closure. HE\u2009+\u2009BMP2 showed virtually complete bone fusion. Collagen fibril birefringence pattern (red color) under polarized light indicated high organization in BMP2-induced newly formed bone (NFB) in HE-supplemented group (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.05). Clear changes in osteocyte lacunae as well as a statistically significant increase in osteoclasts were found around NFB in HE-treated rats. A significant increase in trabecular volume and thickness, and trabecular and cortical density was found in femurs of HE-supplemented rats (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.05). Our findings show, for the first time, that dietary HE has a remarkable modulatory role in the function of locally delivered high-dose BMP2 in bone regeneration possibly via control of inflammation, osteogenesis, changes in osteocyte and osteoclast function and collagen maturation in regenerated and native bone. In conclusion, HE had a significant skeletal bone sparing effect and the ability to provide a more effective BMP-induced craniofacial regeneration.\n                  <\/jats:p>","DOI":"10.1038\/s41598-024-52566-7","type":"journal-article","created":{"date-parts":[[2024,1,31]],"date-time":"2024-01-31T10:02:39Z","timestamp":1706695359000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Mitigation of BMP-induced inflammation in craniofacial bone regeneration and improvement of bone parameters by dietary hesperidin"],"prefix":"10.1038","volume":"14","author":[{"given":"Patricia A.","family":"Miguez","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vin\u00edcius","family":"de Paiva Gon\u00e7alves","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta L.","family":"Musskopf","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angeliz","family":"Rivera-Concepcion","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Skylar","family":"McGaughey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christina","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dong Joon","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen A.","family":"Tuin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aya","family":"Ali","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,1,31]]},"reference":[{"key":"52566_CR1","doi-asserted-by":"publisher","first-page":"1735","DOI":"10.1089\/ten.TEA.2010.0446","volume":"17","author":"KV Brown","year":"2011","unstructured":"Brown, K. V. et al. Improving bone formation in a rat femur segmental defect by controlling bone morphogenetic protein-2 release. Tissue Eng. Part A 17, 1735\u20131746. https:\/\/doi.org\/10.1089\/ten.TEA.2010.0446 (2011).","journal-title":"Tissue Eng. Part A"},{"key":"52566_CR2","doi-asserted-by":"publisher","first-page":"203","DOI":"10.1038\/nrendo.2016.12","volume":"12","author":"VS Salazar","year":"2016","unstructured":"Salazar, V. S., Gamer, L. W. & Rosen, V. BMP signalling in skeletal development, disease and repair. Nat. Rev. Endocrinol. 12, 203\u2013221. https:\/\/doi.org\/10.1038\/nrendo.2016.12 (2016).","journal-title":"Nat. Rev. Endocrinol."},{"key":"52566_CR3","doi-asserted-by":"publisher","first-page":"155","DOI":"10.1007\/s13770-020-00290-4","volume":"18","author":"HJ Son","year":"2021","unstructured":"Son, H. J. et al. Bone generation following repeated administration of recombinant bone morphogenetic protein 2. Tissue Eng. Regen. Med. 18, 155\u2013164. https:\/\/doi.org\/10.1007\/s13770-020-00290-4 (2021).","journal-title":"Tissue Eng. Regen. Med."},{"key":"52566_CR4","doi-asserted-by":"publisher","first-page":"871","DOI":"10.1007\/s13770-022-00457-1","volume":"19","author":"JJ Han","year":"2022","unstructured":"Han, J. J., Yang, H. J. & Hwang, S. J. Enhanced bone regeneration by bone morphogenetic protein-2 after pretreatment with low-intensity pulsed ultrasound in distraction osteogenesis. Tissue Eng. Regen. Med. 19, 871\u2013886. https:\/\/doi.org\/10.1007\/s13770-022-00457-1 (2022).","journal-title":"Tissue Eng. Regen. Med."},{"key":"52566_CR5","doi-asserted-by":"publisher","DOI":"10.3390\/ijms222011121","author":"H Seok","year":"2021","unstructured":"Seok, H., Kim, H. Y., Kang, D. C., Park, J. H. & Park, J. H. Comparison of bone regeneration in different forms of bovine bone scaffolds with recombinant human bone morphogenetic protein-2. Int. J. Mol. Sci. https:\/\/doi.org\/10.3390\/ijms222011121 (2021).","journal-title":"Int. J. Mol. Sci."},{"key":"52566_CR6","doi-asserted-by":"publisher","first-page":"284","DOI":"10.1089\/ten.TEB.2015.0357","volume":"22","author":"AW James","year":"2016","unstructured":"James, A. W. et al. A review of the clinical side effects of bone morphogenetic protein-2. Tissue Eng. Part B Rev. 22, 284\u2013297. https:\/\/doi.org\/10.1089\/ten.TEB.2015.0357 (2016).","journal-title":"Tissue Eng. Part B Rev."},{"key":"52566_CR7","doi-asserted-by":"publisher","DOI":"10.1016\/j.msec.2021.112466","volume":"130","author":"CE Gillman","year":"2021","unstructured":"Gillman, C. E. & Jayasuriya, A. C. FDA-approved bone grafts and bone graft substitute devices in bone regeneration. Mater. Sci. Eng. C Mater. Biol. Appl. 130, 112466. https:\/\/doi.org\/10.1016\/j.msec.2021.112466 (2021).","journal-title":"Mater. Sci. Eng. C Mater. Biol. Appl."},{"key":"52566_CR8","doi-asserted-by":"publisher","DOI":"10.3390\/jdb8030019","author":"D Halloran","year":"2020","unstructured":"Halloran, D., Durbano, H. W. & Nohe, A. Bone morphogenetic protein-2 in development and bone homeostasis. J. Dev. Biol. https:\/\/doi.org\/10.3390\/jdb8030019 (2020).","journal-title":"J. Dev. Biol."},{"key":"52566_CR9","doi-asserted-by":"publisher","first-page":"262","DOI":"10.1016\/j.bbrc.2011.01.022","volume":"405","author":"PA Miguez","year":"2011","unstructured":"Miguez, P. A., Terajima, M., Nagaoka, H., Mochida, Y. & Yamauchi, M. Role of glycosaminoglycans of biglycan in BMP-2 signaling. Biochem. Biophys. Res. Commun. 405, 262\u2013266. https:\/\/doi.org\/10.1016\/j.bbrc.2011.01.022 (2011).","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"52566_CR10","doi-asserted-by":"publisher","first-page":"406","DOI":"10.1177\/0022034514521237","volume":"93","author":"PA Miguez","year":"2014","unstructured":"Miguez, P. A. et al. Recombinant biglycan promotes bone morphogenetic protein-induced osteogenesis. J. Dent. Res. 93, 406\u2013411. https:\/\/doi.org\/10.1177\/0022034514521237 (2014).","journal-title":"J. Dent. Res."},{"key":"52566_CR11","doi-asserted-by":"publisher","first-page":"7022","DOI":"10.1038\/s41598-018-25279-x","volume":"8","author":"P Jongwattanapisan","year":"2018","unstructured":"Jongwattanapisan, P. et al. Identification of the effector domain of biglycan that facilitates BMP-2 osteogenic function. Sci. Rep. 8, 7022. https:\/\/doi.org\/10.1038\/s41598-018-25279-x (2018).","journal-title":"Sci. Rep."},{"key":"52566_CR12","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22063223","author":"PA Miguez","year":"2021","unstructured":"Miguez, P. A. et al. Hesperidin promotes osteogenesis and modulates collagen matrix organization and mineralization in vitro and in vivo. Int. J. Mol. Sci. https:\/\/doi.org\/10.3390\/ijms22063223 (2021).","journal-title":"Int. J. Mol. Sci."},{"key":"52566_CR13","doi-asserted-by":"publisher","first-page":"613","DOI":"10.1080\/10408398.2014.906382","volume":"57","author":"C Li","year":"2017","unstructured":"Li, C. & Schluesener, H. Health-promoting effects of the citrus flavanone hesperidin. Crit. Rev. Food. Sci. Nutr. 57, 613\u2013631. https:\/\/doi.org\/10.1080\/10408398.2014.906382 (2017).","journal-title":"Crit. Rev. Food. Sci. Nutr."},{"key":"52566_CR14","doi-asserted-by":"publisher","first-page":"442","DOI":"10.1080\/10799893.2020.1752718","volume":"40","author":"W Hong","year":"2020","unstructured":"Hong, W. & Zhang, W. Hesperidin promotes differentiation of alveolar osteoblasts via Wnt\/\u03b2-Catenin signaling pathway. J. Recept. Signal Transduct. Res. 40, 442\u2013448. https:\/\/doi.org\/10.1080\/10799893.2020.1752718 (2020).","journal-title":"J. Recept. Signal Transduct. Res."},{"key":"52566_CR15","doi-asserted-by":"publisher","DOI":"10.3390\/nu14122387","author":"K Pyrzynska","year":"2022","unstructured":"Pyrzynska, K. Hesperidin: a review on extraction methods, stability and biological activities. Nutrients https:\/\/doi.org\/10.3390\/nu14122387 (2022).","journal-title":"Nutrients"},{"key":"52566_CR16","doi-asserted-by":"publisher","first-page":"424","DOI":"10.1016\/j.jnutbio.2009.01.017","volume":"21","author":"A Trzeciakiewicz","year":"2010","unstructured":"Trzeciakiewicz, A. et al. Hesperetin stimulates differentiation of primary rat osteoblasts involving the BMP signalling pathway. J. Nutr. Biochem. 21, 424\u2013431. https:\/\/doi.org\/10.1016\/j.jnutbio.2009.01.017 (2010).","journal-title":"J. Nutr. Biochem."},{"key":"52566_CR17","doi-asserted-by":"publisher","first-page":"21031","DOI":"10.18632\/oncotarget.15473","volume":"8","author":"D Xue","year":"2017","unstructured":"Xue, D. et al. The role of hesperetin on osteogenesis of human mesenchymal stem cells and its function in bone regeneration. Oncotarget 8, 21031\u201321043. https:\/\/doi.org\/10.18632\/oncotarget.15473 (2017).","journal-title":"Oncotarget"},{"key":"52566_CR18","doi-asserted-by":"publisher","first-page":"187","DOI":"10.1080\/15384101.2021.2015668","volume":"21","author":"S Yuan","year":"2022","unstructured":"Yuan, S., Zhang, C. & Wang, B. Neohesperidin promotes the proliferation and osteogenic differentiation of BMSCs via BMP2-Wnt\/\u03b2-catenin pathway. Cell Cycle 21, 187\u2013201. https:\/\/doi.org\/10.1080\/15384101.2021.2015668 (2022).","journal-title":"Cell Cycle"},{"key":"52566_CR19","doi-asserted-by":"publisher","first-page":"1108","DOI":"10.1016\/j.bone.2011.07.030","volume":"49","author":"V Habauzit","year":"2011","unstructured":"Habauzit, V. et al. Differential effects of two citrus flavanones on bone quality in senescent male rats in relation to their bioavailability and metabolism. Bone 49, 1108\u20131116. https:\/\/doi.org\/10.1016\/j.bone.2011.07.030 (2011).","journal-title":"Bone"},{"key":"52566_CR20","doi-asserted-by":"publisher","first-page":"648","DOI":"10.1152\/japplphysiol.00441.2007","volume":"104","author":"MN Horcajada","year":"2008","unstructured":"Horcajada, M. N. et al. Hesperidin inhibits ovariectomized-induced osteopenia and shows differential effects on bone mass and strength in young and adult intact rats. J. Appl. Physiol. (Bethesda, Md.\u202f: 1985) 104, 648\u2013654. https:\/\/doi.org\/10.1152\/japplphysiol.00441.2007 (2008).","journal-title":"J. Appl. Physiol. (Bethesda, Md. : 1985)"},{"key":"52566_CR21","doi-asserted-by":"publisher","first-page":"976","DOI":"10.1017\/s0007114509338830","volume":"102","author":"V Habauzit","year":"2009","unstructured":"Habauzit, V. et al. Increased bioavailability of hesperetin-7-glucoside compared with hesperidin results in more efficient prevention of bone loss in adult ovariectomised rats. Br. J. Nutr. 102, 976\u2013984. https:\/\/doi.org\/10.1017\/s0007114509338830 (2009).","journal-title":"Br. J. Nutr."},{"key":"52566_CR22","doi-asserted-by":"publisher","first-page":"289","DOI":"10.1002\/ptr.5001","volume":"28","author":"H Chiba","year":"2014","unstructured":"Chiba, H. et al. Hesperidin prevents androgen deficiency-induced bone loss in male mice. Phytother. Res. PTR 28, 289\u2013295. https:\/\/doi.org\/10.1002\/ptr.5001 (2014).","journal-title":"Phytother. Res. PTR"},{"key":"52566_CR23","doi-asserted-by":"publisher","DOI":"10.3390\/dj8030086","author":"JM Souza Jr","year":"2020","unstructured":"Souza, J. M. Jr. et al. Effect of flavonoid supplementation on alveolar bone healing-a randomized pilot trial. Dent. J. (Basel) https:\/\/doi.org\/10.3390\/dj8030086 (2020).","journal-title":"Dent. J. (Basel)"},{"key":"52566_CR24","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.1000412","volume":"8","author":"C Kilkenny","year":"2010","unstructured":"Kilkenny, C., Browne, W. J., Cuthill, I. C., Emerson, M. & Altman, D. G. Improving bioscience research reporting: The ARRIVE guidelines for reporting animal research. PLoS Biol. 8, e1000412. https:\/\/doi.org\/10.1371\/journal.pbio.1000412 (2010).","journal-title":"PLoS Biol."},{"key":"52566_CR25","doi-asserted-by":"publisher","DOI":"10.3390\/ijms23137100","author":"VP Gon\u00e7alves","year":"2022","unstructured":"Gon\u00e7alves, V. P. et al. Systemic dietary hesperidin modulation of osteoclastogenesis, bone homeostasis and periodontal disease in mice. Int. J. Mol. Sci. https:\/\/doi.org\/10.3390\/ijms23137100 (2022).","journal-title":"Int. J. Mol. Sci."},{"key":"52566_CR26","doi-asserted-by":"publisher","first-page":"291","DOI":"10.15412\/j.Bcn.03070402","volume":"7","author":"T Naserpour Farivar","year":"2016","unstructured":"Naserpour Farivar, T., Nassiri-Asl, M., Johari, P., Najafipour, R. & Hajiali, F. The effects of kainic acid-induced seizure on gene expression of brain neurotransmitter receptors in mice using RT(2) PCR array. Basic Clin. Neurosci. 7, 291\u2013298. https:\/\/doi.org\/10.15412\/j.Bcn.03070402 (2016).","journal-title":"Basic Clin. Neurosci."},{"key":"52566_CR27","doi-asserted-by":"publisher","first-page":"384","DOI":"10.1111\/cid.12094","volume":"17","author":"J Reside","year":"2015","unstructured":"Reside, J. et al. In vivo assessment of bone healing following Piezotome\u00ae ultrasonic instrumentation. Clin. Implant. Dent. Relat. Res. 17, 384\u2013394. https:\/\/doi.org\/10.1111\/cid.12094 (2015).","journal-title":"Clin. Implant. Dent. Relat. Res."},{"key":"52566_CR28","doi-asserted-by":"publisher","first-page":"1468","DOI":"10.1002\/jbmr.141","volume":"25","author":"ML Bouxsein","year":"2010","unstructured":"Bouxsein, M. L. et al. Guidelines for assessment of bone microstructure in rodents using micro-computed tomography. J. Bone Miner. Res. 25, 1468\u20131486. https:\/\/doi.org\/10.1002\/jbmr.141 (2010).","journal-title":"J. Bone Miner. Res."},{"key":"52566_CR29","doi-asserted-by":"publisher","first-page":"71","DOI":"10.1002\/mus.24998","volume":"54","author":"LR Smith","year":"2016","unstructured":"Smith, L. R., Hammers, D. W., Sweeney, H. L. & Barton, E. R. Increased collagen cross-linking is a signature of dystrophin-deficient muscle. Muscle Nerve 54, 71\u201378. https:\/\/doi.org\/10.1002\/mus.24998 (2016).","journal-title":"Muscle Nerve"},{"key":"52566_CR30","doi-asserted-by":"publisher","DOI":"10.3390\/ijms232012204","author":"H Shen","year":"2022","unstructured":"Shen, H. et al. Osteoclast-driven osteogenesis, bone remodeling and biomaterial resorption: A new profile of BMP2-CPC-induced alveolar bone regeneration. Int. J. Mol. Sci. https:\/\/doi.org\/10.3390\/ijms232012204 (2022).","journal-title":"Int. J. Mol. Sci."},{"key":"52566_CR31","doi-asserted-by":"publisher","first-page":"1231","DOI":"10.1002\/jbm.a.36897","volume":"108","author":"S Injamuri","year":"2020","unstructured":"Injamuri, S., Rahaman, M. N., Shen, Y. & Huang, Y. W. Relaxin enhances bone regeneration with BMP-2-loaded hydroxyapatite microspheres. J. Biomed. Mater. Res. A 108, 1231\u20131242. https:\/\/doi.org\/10.1002\/jbm.a.36897 (2020).","journal-title":"J. Biomed. Mater. Res. A"},{"key":"52566_CR32","doi-asserted-by":"publisher","first-page":"3245","DOI":"10.1016\/j.biomaterials.2008.04.031","volume":"29","author":"DH Kempen","year":"2008","unstructured":"Kempen, D. H. et al. Retention of in vitro and in vivo BMP-2 bioactivities in sustained delivery vehicles for bone tissue engineering. Biomaterials 29, 3245\u20133252. https:\/\/doi.org\/10.1016\/j.biomaterials.2008.04.031 (2008).","journal-title":"Biomaterials"},{"key":"52566_CR33","doi-asserted-by":"publisher","first-page":"765","DOI":"10.1016\/j.joms.2011.09.008","volume":"70","author":"EJ Woo","year":"2012","unstructured":"Woo, E. J. Adverse events reported after the use of recombinant human bone morphogenetic protein 2. J. Oral Maxillofac. Surg. 70, 765\u2013767. https:\/\/doi.org\/10.1016\/j.joms.2011.09.008 (2012).","journal-title":"J. Oral Maxillofac. Surg."},{"key":"52566_CR34","doi-asserted-by":"publisher","first-page":"3220","DOI":"10.1016\/j.biomaterials.2013.12.087","volume":"35","author":"CJ Kowalczewski","year":"2014","unstructured":"Kowalczewski, C. J. et al. Reduction of ectopic bone growth in critically-sized rat mandible defects by delivery of rhBMP-2 from kerateine biomaterials. Biomaterials 35, 3220\u20133228. https:\/\/doi.org\/10.1016\/j.biomaterials.2013.12.087 (2014).","journal-title":"Biomaterials"},{"key":"52566_CR35","doi-asserted-by":"publisher","first-page":"10818","DOI":"10.1007\/s11356-020-11327-5","volume":"28","author":"M Kuzu","year":"2021","unstructured":"Kuzu, M., Kandemir, F. M., Y\u0131ld\u0131r\u0131m, S., \u00c7a\u011flayan, C. & K\u00fc\u00e7\u00fckler, S. Attenuation of sodium arsenite-induced cardiotoxicity and neurotoxicity with the antioxidant, anti-inflammatory, and antiapoptotic effects of hesperidin. Environ. Sci. Pollut. Res. Int. 28, 10818\u201310831. https:\/\/doi.org\/10.1007\/s11356-020-11327-5 (2021).","journal-title":"Environ. Sci. Pollut. Res. Int."},{"key":"52566_CR36","doi-asserted-by":"publisher","first-page":"199","DOI":"10.1097\/BPO.0b013e3181cec35b","volume":"30","author":"KM MacDonald","year":"2010","unstructured":"MacDonald, K. M. et al. Exaggerated inflammatory response after use of recombinant bone morphogenetic protein in recurrent unicameral bone cysts. J. Pediatr. Orthop. 30, 199\u2013205. https:\/\/doi.org\/10.1097\/BPO.0b013e3181cec35b (2010).","journal-title":"J. Pediatr. Orthop."},{"key":"52566_CR37","doi-asserted-by":"publisher","first-page":"E149","DOI":"10.1097\/BRS.0b013e3181f2d1ec","volume":"36","author":"KB Lee","year":"2011","unstructured":"Lee, K. B. et al. Inflammatory characteristics of rhBMP-2 in vitro and in an in vivo rodent model. Spine (Phila Pa 1976) 36, E149-154. https:\/\/doi.org\/10.1097\/BRS.0b013e3181f2d1ec (2011).","journal-title":"Spine (Phila Pa 1976)"},{"key":"52566_CR38","doi-asserted-by":"publisher","first-page":"316","DOI":"10.1016\/j.jhsa.2011.10.007","volume":"37","author":"AW Ritting","year":"2012","unstructured":"Ritting, A. W., Weber, E. W. & Lee, M. C. Exaggerated inflammatory response and bony resorption from BMP-2 use in a pediatric forearm nonunion. J. Hand Surg. Am. 37, 316\u2013321. https:\/\/doi.org\/10.1016\/j.jhsa.2011.10.007 (2012).","journal-title":"J. Hand Surg. Am."},{"key":"52566_CR39","doi-asserted-by":"publisher","first-page":"1452","DOI":"10.1097\/BRS.0b013e31828a3504","volume":"38","author":"M Wang","year":"2013","unstructured":"Wang, M. et al. Minimizing the severity of rhBMP-2-induced inflammation and heterotopic ossification with a polyelectrolyte carrier incorporating heparin on microbead templates. Spine (Phila Pa 1976) 38, 1452\u20131458. https:\/\/doi.org\/10.1097\/BRS.0b013e31828a3504 (2013).","journal-title":"Spine (Phila Pa 1976)"},{"key":"52566_CR40","doi-asserted-by":"publisher","first-page":"1640","DOI":"10.1097\/BRS.0b013e31829cf348","volume":"38","author":"C Xiong","year":"2013","unstructured":"Xiong, C. et al. BMP-2 adverse reactions treated with human dose equivalent dexamethasone in a rodent model of soft-tissue inflammation. Spine (Phila Pa 1976) 38, 1640\u20131647. https:\/\/doi.org\/10.1097\/BRS.0b013e31829cf348 (2013).","journal-title":"Spine (Phila Pa 1976)"},{"key":"52566_CR41","doi-asserted-by":"publisher","first-page":"1186","DOI":"10.1016\/j.joca.2014.06.017","volume":"22","author":"RL Huang","year":"2014","unstructured":"Huang, R. L., Yuan, Y., Tu, J., Zou, G. M. & Li, Q. Exaggerated inflammatory environment decreases BMP-2\/ACS-induced ectopic bone mass in a rat model: implications for clinical use of BMP-2. Osteoarthr. Cartil. 22, 1186\u20131196. https:\/\/doi.org\/10.1016\/j.joca.2014.06.017 (2014).","journal-title":"Osteoarthr. Cartil."},{"key":"52566_CR42","doi-asserted-by":"publisher","first-page":"723","DOI":"10.17179\/excli2019-1094","volume":"18","author":"Z Zhou","year":"2019","unstructured":"Zhou, Z., Kandhare, A. D., Kandhare, A. A. & Bodhankar, S. L. Hesperidin ameliorates bleomycin-induced experimental pulmonary fibrosis via inhibition of TGF-beta1\/Smad3\/AMPK and IkappaBalpha\/NF-kappaB pathways. EXCLI J. 18, 723\u2013745. https:\/\/doi.org\/10.17179\/excli2019-1094 (2019).","journal-title":"EXCLI J."},{"key":"52566_CR43","doi-asserted-by":"publisher","first-page":"132","DOI":"10.1016\/j.burns.2021.04.016","volume":"48","author":"M Vabeiryureilai","year":"2022","unstructured":"Vabeiryureilai, M., Lalrinzuali, K. & Jagetia, G. C. NF-\u03baB and COX-2 repression with topical application of hesperidin and naringin hydrogels augments repair and regeneration of deep dermal wounds. Burns 48, 132\u2013145. https:\/\/doi.org\/10.1016\/j.burns.2021.04.016 (2022).","journal-title":"Burns"},{"key":"52566_CR44","doi-asserted-by":"publisher","first-page":"6269","DOI":"10.1021\/acs.jafc.8b00959","volume":"66","author":"KW Ruiz-Miyazawa","year":"2018","unstructured":"Ruiz-Miyazawa, K. W. et al. Hesperidin methylchalcone suppresses experimental gout arthritis in mice by inhibiting NF-\u03baB activation. J. Agric. Food Chem. 66, 6269\u20136280. https:\/\/doi.org\/10.1021\/acs.jafc.8b00959 (2018).","journal-title":"J. Agric. Food Chem."},{"key":"52566_CR45","doi-asserted-by":"publisher","DOI":"10.3390\/cells8121636","author":"E Jimi","year":"2019","unstructured":"Jimi, E., Takakura, N., Hiura, F., Nakamura, I. & Hirata-Tsuchiya, S. The role of NF-\u03baB in physiological bone development and inflammatory bone diseases: Is NF-\u03baB inhibition \u201ckilling two birds with one stone\u201d?. Cells https:\/\/doi.org\/10.3390\/cells8121636 (2019).","journal-title":"Cells"},{"key":"52566_CR46","doi-asserted-by":"publisher","first-page":"161","DOI":"10.1042\/bcj20210547","volume":"479","author":"M Haga","year":"2022","unstructured":"Haga, M. & Okada, M. Systems approaches to investigate the role of NF-\u03baB signaling in aging. Biochem. J. 479, 161\u2013183. https:\/\/doi.org\/10.1042\/bcj20210547 (2022).","journal-title":"Biochem. J."},{"key":"52566_CR47","doi-asserted-by":"publisher","first-page":"E131","DOI":"10.1152\/ajpendo.00347.2013","volume":"306","author":"SJ Burke","year":"2014","unstructured":"Burke, S. J. et al. NF-\u03baB and STAT1 control CXCL1 and CXCL2 gene transcription. Am. J. Physiol. Endocrinol. Metab. 306, E131-149. https:\/\/doi.org\/10.1152\/ajpendo.00347.2013 (2014).","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"52566_CR48","doi-asserted-by":"publisher","first-page":"1457","DOI":"10.1002\/jbmr.1866","volume":"28","author":"H Nakamura","year":"2013","unstructured":"Nakamura, H. et al. Disruption of NF-\u03baB1 prevents bone loss caused by mechanical unloading. J. Bone Miner. Res. 28, 1457\u20131467. https:\/\/doi.org\/10.1002\/jbmr.1866 (2013).","journal-title":"J. Bone Miner. Res."},{"key":"52566_CR49","doi-asserted-by":"publisher","DOI":"10.3390\/ijms23147995","author":"E Jimi","year":"2022","unstructured":"Jimi, E. & Katagiri, T. Critical roles of NF-\u03baB signaling molecules in bone metabolism revealed by genetic mutations in osteopetrosis. Int. J. Mol. Sci. https:\/\/doi.org\/10.3390\/ijms23147995 (2022).","journal-title":"Int. J. Mol. Sci."},{"key":"52566_CR50","doi-asserted-by":"publisher","first-page":"184","DOI":"10.1016\/j.bcp.2006.04.018","volume":"72","author":"S Bandyopadhyay","year":"2006","unstructured":"Bandyopadhyay, S. et al. Attenuation of osteoclastogenesis and osteoclast function by apigenin. Biochem. Pharmacol. 72, 184\u2013197. https:\/\/doi.org\/10.1016\/j.bcp.2006.04.018 (2006).","journal-title":"Biochem. Pharmacol."},{"key":"52566_CR51","doi-asserted-by":"publisher","first-page":"1150","DOI":"10.1016\/j.intimp.2011.03.012","volume":"11","author":"M Funakoshi-Tago","year":"2011","unstructured":"Funakoshi-Tago, M., Nakamura, K., Tago, K., Mashino, T. & Kasahara, T. Anti-inflammatory activity of structurally related flavonoids, Apigenin Luteolin and Fisetin. Int. Immunopharmacol. 11, 1150\u20131159. https:\/\/doi.org\/10.1016\/j.intimp.2011.03.012 (2011).","journal-title":"Int. Immunopharmacol."},{"key":"52566_CR52","doi-asserted-by":"publisher","first-page":"337","DOI":"10.1016\/j.bcp.2015.06.013","volume":"96","author":"H Lim","year":"2015","unstructured":"Lim, H., Park, H. & Kim, H. P. Effects of flavonoids on senescence-associated secretory phenotype formation from bleomycin-induced senescence in BJ fibroblasts. Biochem. Pharmacol. 96, 337\u2013348. https:\/\/doi.org\/10.1016\/j.bcp.2015.06.013 (2015).","journal-title":"Biochem. Pharmacol."},{"key":"52566_CR53","doi-asserted-by":"publisher","first-page":"9794625","DOI":"10.1155\/2018\/9794625","volume":"2018","author":"A Riaz","year":"2018","unstructured":"Riaz, A. et al. Astragalin: A bioactive phytochemical with potential therapeutic activities. Adv. Pharmacol. Sci. 2018, 9794625. https:\/\/doi.org\/10.1155\/2018\/9794625 (2018).","journal-title":"Adv. Pharmacol. Sci."},{"key":"52566_CR54","doi-asserted-by":"publisher","first-page":"3220","DOI":"10.3892\/ijmm.2018.3903","volume":"42","author":"SP Xu","year":"2018","unstructured":"Xu, S. P. & Li, Y. S. Fisetin inhibits pristine-induced systemic lupus erythematosus in a murine model through CXCLs regulation. Int. J. Mol. Med. 42, 3220\u20133230. https:\/\/doi.org\/10.3892\/ijmm.2018.3903 (2018).","journal-title":"Int. J. Mol. Med."},{"key":"52566_CR55","doi-asserted-by":"publisher","DOI":"10.3390\/nu11030648","author":"T Muhammad","year":"2019","unstructured":"Muhammad, T., Ikram, M., Ullah, R., Rehman, S. U. & Kim, M. O. Hesperetin, a citrus flavonoid, attenuates LPS-induced neuroinflammation, apoptosis and memory impairments by modulating TLR4\/NF-\u03baB signaling. Nutrients https:\/\/doi.org\/10.3390\/nu11030648 (2019).","journal-title":"Nutrients"},{"key":"52566_CR56","doi-asserted-by":"publisher","first-page":"1697","DOI":"10.1002\/ptr.6358","volume":"33","author":"H Xuguang","year":"2019","unstructured":"Xuguang, H. et al. Hesperidin ameliorates insulin resistance by regulating the IRS1-GLUT2 pathway via TLR4 in HepG2 cells. Phytother. Res. 33, 1697\u20131705. https:\/\/doi.org\/10.1002\/ptr.6358 (2019).","journal-title":"Phytother. Res."},{"key":"52566_CR57","doi-asserted-by":"publisher","first-page":"6987","DOI":"10.2147\/ott.S261033","volume":"13","author":"XB Jia","year":"2020","unstructured":"Jia, X. B., Zhang, Q., Xu, L., Yao, W. J. & Wei, L. Effect of Malus asiatica Nakai leaf flavonoids on the prevention of esophageal cancer in C57BL\/6J mice by regulating the IL-17 signaling pathway. Onco Targets Ther. 13, 6987\u20136996. https:\/\/doi.org\/10.2147\/ott.S261033 (2020).","journal-title":"Onco Targets Ther."},{"key":"52566_CR58","doi-asserted-by":"publisher","DOI":"10.1080\/09603123.2022.2093841","author":"Y Buzda\u011fl\u0131","year":"2022","unstructured":"Buzda\u011fl\u0131, Y., Eyip\u0131nar, C. D., Kac\u0131, F. N. & Tekin, A. Effects of hesperidin on anti-inflammatory and antioxidant response in healthy people: A meta-analysis and meta-regression. Int. J. Environ. Health Res. https:\/\/doi.org\/10.1080\/09603123.2022.2093841 (2022).","journal-title":"Int. J. Environ. Health Res."},{"key":"52566_CR59","doi-asserted-by":"publisher","DOI":"10.3390\/nu14010067","author":"CF Tsai","year":"2021","unstructured":"Tsai, C. F. et al. Regulatory effects of quercetin on M1\/M2 macrophage polarization and oxidative\/antioxidative balance. Nutrients https:\/\/doi.org\/10.3390\/nu14010067 (2021).","journal-title":"Nutrients"},{"key":"52566_CR60","doi-asserted-by":"publisher","first-page":"621","DOI":"10.1007\/s00223-014-9843-x","volume":"94","author":"SW Volk","year":"2014","unstructured":"Volk, S. W. et al. Type III collagen regulates osteoblastogenesis and the quantity of trabecular bone. Calcif. Tissue Int. 94, 621\u2013631. https:\/\/doi.org\/10.1007\/s00223-014-9843-x (2014).","journal-title":"Calcif. Tissue Int."},{"key":"52566_CR61","doi-asserted-by":"publisher","first-page":"215","DOI":"10.1111\/wrr.12398","volume":"24","author":"MK Lichtman","year":"2016","unstructured":"Lichtman, M. K., Otero-Vinas, M. & Falanga, V. Transforming growth factor beta (TGF-\u03b2) isoforms in wound healing and fibrosis. Wound Repair Regen. 24, 215\u2013222. https:\/\/doi.org\/10.1111\/wrr.12398 (2016).","journal-title":"Wound Repair Regen."},{"key":"52566_CR62","doi-asserted-by":"publisher","first-page":"199","DOI":"10.5115\/acb.2016.49.3.199","volume":"49","author":"CY Yun","year":"2016","unstructured":"Yun, C. Y. et al. Requirement of Smad4-mediated signaling in odontoblast differentiation and dentin matrix formation. Anat. Cell Biol. 49, 199\u2013205. https:\/\/doi.org\/10.5115\/acb.2016.49.3.199 (2016).","journal-title":"Anat. Cell Biol."},{"key":"52566_CR63","doi-asserted-by":"publisher","first-page":"415","DOI":"10.1080\/09205063.2019.1571397","volume":"30","author":"A Alici-Garipcan","year":"2019","unstructured":"Alici-Garipcan, A. et al. Critical-size alveolar defect treatment via TGF-\u00df3 and BMP-2 releasing hybrid constructs. J. Biomater. Sci. Polym. Ed. 30, 415\u2013436. https:\/\/doi.org\/10.1080\/09205063.2019.1571397 (2019).","journal-title":"J. Biomater. Sci. Polym. Ed."},{"issue":"472","key":"52566_CR64","doi-asserted-by":"publisher","first-page":"e479","DOI":"10.1016\/j.avsg.2019.05.057","volume":"61","author":"SL Olson","year":"2019","unstructured":"Olson, S. L., Murray, M. L. & Skeik, N. A novel frameshift COL3A1 variant in vascular Ehlers\u2013Danlos syndrome. Ann. Vasc. Surg. 61(472), e479-472.e413. https:\/\/doi.org\/10.1016\/j.avsg.2019.05.057 (2019).","journal-title":"Ann. Vasc. Surg."},{"key":"52566_CR65","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.246934","author":"T Mang","year":"2020","unstructured":"Mang, T. et al. BMPR1A is necessary for chondrogenesis and osteogenesis, whereas BMPR1B prevents hypertrophic differentiation. J. Cell Sci. https:\/\/doi.org\/10.1242\/jcs.246934 (2020).","journal-title":"J. Cell Sci."},{"key":"52566_CR66","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.abb4416","author":"T Maruyama","year":"2021","unstructured":"Maruyama, T. et al. BMPR1A maintains skeletal stem cell properties in craniofacial development and craniosynostosis. Sci. Transl. Med. https:\/\/doi.org\/10.1126\/scitranslmed.abb4416 (2021).","journal-title":"Sci. Transl. Med."},{"key":"52566_CR67","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0204384","volume":"14","author":"F Ye","year":"2019","unstructured":"Ye, F. et al. The role of BMP6 in the proliferation and differentiation of chicken cartilage cells. PLoS One 14, e0204384. https:\/\/doi.org\/10.1371\/journal.pone.0204384 (2019).","journal-title":"PLoS One"},{"key":"52566_CR68","doi-asserted-by":"publisher","DOI":"10.3389\/fmolb.2021.593310","volume":"8","author":"ML Zou","year":"2021","unstructured":"Zou, M. L. et al. The smad dependent TGF-\u03b2 and BMP signaling pathway in bone remodeling and therapies. Front. Mol. Biosci. 8, 593310. https:\/\/doi.org\/10.3389\/fmolb.2021.593310 (2021).","journal-title":"Front. Mol. Biosci."},{"key":"52566_CR69","doi-asserted-by":"publisher","first-page":"1119368","DOI":"10.3389\/fphys.2023.1119368","volume":"14","author":"R Shainer","year":"2023","unstructured":"Shainer, R. et al. Biglycan regulates bone development and regeneration. Front. Physiol. 14, 1119368. https:\/\/doi.org\/10.3389\/fphys.2023.1119368 (2023).","journal-title":"Front. Physiol."},{"key":"52566_CR70","doi-asserted-by":"publisher","first-page":"747","DOI":"10.1369\/0022155420937371","volume":"68","author":"V Kram","year":"2020","unstructured":"Kram, V. et al. Biglycan in the skeleton. J. Histochem. Cytochem. 68, 747\u2013762. https:\/\/doi.org\/10.1369\/0022155420937371 (2020).","journal-title":"J. Histochem. Cytochem."},{"key":"52566_CR71","doi-asserted-by":"publisher","first-page":"963","DOI":"10.1369\/0022155412456380","volume":"60","author":"MV Nastase","year":"2012","unstructured":"Nastase, M. V., Young, M. F. & Schaefer, L. Biglycan: A multivalent proteoglycan providing structure and signals. J. Histochem. Cytochem. 60, 963\u2013975. https:\/\/doi.org\/10.1369\/0022155412456380 (2012).","journal-title":"J. Histochem. Cytochem."},{"key":"52566_CR72","doi-asserted-by":"publisher","first-page":"156","DOI":"10.1124\/jpet.117.244483","volume":"365","author":"MA Rostam","year":"2018","unstructured":"Rostam, M. A. et al. Flavopiridol inhibits TGF-\u03b2-stimulated biglycan synthesis by blocking linker region phosphorylation and nuclear translocation of Smad2. J. Pharmacol. Exp. Ther. 365, 156\u2013164. https:\/\/doi.org\/10.1124\/jpet.117.244483 (2018).","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"52566_CR73","doi-asserted-by":"publisher","first-page":"9646","DOI":"10.18632\/aging.202708","volume":"13","author":"Y Shao","year":"2021","unstructured":"Shao, Y. et al. BMP5 silencing inhibits chondrocyte senescence and apoptosis as well as osteoarthritis progression in mice. Aging (Albany NY) 13, 9646\u20139664. https:\/\/doi.org\/10.18632\/aging.202708 (2021).","journal-title":"Aging (Albany NY)"},{"key":"52566_CR74","doi-asserted-by":"publisher","DOI":"10.1016\/j.gene.2020.145253","volume":"769","author":"H Zhang","year":"2021","unstructured":"Zhang, H. et al. FN1 promotes chondrocyte differentiation and collagen production via TGF-\u03b2\/PI3K\/Akt pathway in mice with femoral fracture. Gene 769, 145253. https:\/\/doi.org\/10.1016\/j.gene.2020.145253 (2021).","journal-title":"Gene"},{"key":"52566_CR75","doi-asserted-by":"publisher","first-page":"3175","DOI":"10.1158\/0008-5472.Can-12-0481","volume":"72","author":"JH Lee","year":"2012","unstructured":"Lee, J. H. et al. CXCL10 promotes osteolytic bone metastasis by enhancing cancer outgrowth and osteoclastogenesis. Cancer Res. 72, 3175\u20133186. https:\/\/doi.org\/10.1158\/0008-5472.Can-12-0481 (2012).","journal-title":"Cancer Res."},{"key":"52566_CR76","doi-asserted-by":"publisher","first-page":"287","DOI":"10.1159\/000445106","volume":"201","author":"S Kreft","year":"2016","unstructured":"Kreft, S. et al. Skin wound repair is not altered in the absence of endogenous AnxA1 or AnxA5, but pharmacological concentrations of AnxA4 and AnxA5 inhibit wound hemostasis. Cells Tissues Organs 201, 287\u2013298. https:\/\/doi.org\/10.1159\/000445106 (2016).","journal-title":"Cells Tissues Organs"},{"key":"52566_CR77","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.217422","author":"BC Subramanian","year":"2018","unstructured":"Subramanian, B. C., Moissoglu, K. & Parent, C. A. The LTB(4)-BLT1 axis regulates the polarized trafficking of chemoattractant GPCRs during neutrophil chemotaxis. J. Cell Sci. https:\/\/doi.org\/10.1242\/jcs.217422 (2018).","journal-title":"J. Cell Sci."},{"key":"52566_CR78","doi-asserted-by":"publisher","first-page":"68","DOI":"10.1016\/s0934-8832(89)80021-6","volume":"9","author":"GE Pi\u00e9rard","year":"1989","unstructured":"Pi\u00e9rard, G. E. Sirius red polarization method is useful to visualize the organization of connective tissues but not the molecular composition of their fibrous polymers. Matrix 9, 68\u201371. https:\/\/doi.org\/10.1016\/s0934-8832(89)80021-6 (1989).","journal-title":"Matrix"},{"key":"52566_CR79","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2021.116242","volume":"154","author":"T Saito","year":"2022","unstructured":"Saito, T. et al. Decrease of lysyl hydroxylase 2 activity causes abnormal collagen molecular phenotypes, defective mineralization and compromised mechanical properties of bone. Bone 154, 116242. https:\/\/doi.org\/10.1016\/j.bone.2021.116242 (2022).","journal-title":"Bone"},{"key":"52566_CR80","doi-asserted-by":"publisher","DOI":"10.3389\/fbioe.2022.918866","volume":"10","author":"W Zhang","year":"2022","unstructured":"Zhang, W. et al. A matter of origin-identification of SEMA3A, BGLAP, SPP1 and PHEX as distinctive molecular features between bone site-specific human osteoblasts on transcription level. Front. Bioeng. Biotechnol. 10, 918866. https:\/\/doi.org\/10.3389\/fbioe.2022.918866 (2022).","journal-title":"Front. Bioeng. Biotechnol."},{"key":"52566_CR81","doi-asserted-by":"publisher","DOI":"10.1016\/j.aanat.2019.151422","volume":"227","author":"FGF Tresguerres","year":"2020","unstructured":"Tresguerres, F. G. F. et al. The osteocyte: A multifunctional cell within the bone. Ann. Anat. 227, 151422. https:\/\/doi.org\/10.1016\/j.aanat.2019.151422 (2020).","journal-title":"Ann. Anat."},{"key":"52566_CR82","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1186\/s40510-018-0216-2","volume":"19","author":"A Singh","year":"2018","unstructured":"Singh, A., Gill, G., Kaur, H., Amhmed, M. & Jakhu, H. Role of osteopontin in bone remodeling and orthodontic tooth movement: A review. Prog. Orthod. 19, 18. https:\/\/doi.org\/10.1186\/s40510-018-0216-2 (2018).","journal-title":"Prog. Orthod."},{"key":"52566_CR83","doi-asserted-by":"publisher","first-page":"194","DOI":"10.1016\/j.actbio.2020.04.040","volume":"120","author":"B Depalle","year":"2021","unstructured":"Depalle, B. et al. Osteopontin regulates type I collagen fibril formation in bone tissue. Acta Biomater. 120, 194\u2013202. https:\/\/doi.org\/10.1016\/j.actbio.2020.04.040 (2021).","journal-title":"Acta Biomater."},{"key":"52566_CR84","doi-asserted-by":"publisher","first-page":"107","DOI":"10.2319\/030911-173.1","volume":"82","author":"JY Kim","year":"2012","unstructured":"Kim, J. Y., Kim, B. I., Jue, S. S., Park, J. H. & Shin, J. W. Localization of osteopontin and osterix in periodontal tissue during orthodontic tooth movement in rats. Angle Orthod. 82, 107\u2013114. https:\/\/doi.org\/10.2319\/030911-173.1 (2012).","journal-title":"Angle Orthod."},{"key":"52566_CR85","doi-asserted-by":"publisher","first-page":"956","DOI":"10.1359\/jbmr.060315","volume":"21","author":"S Fujihara","year":"2006","unstructured":"Fujihara, S. et al. Function and regulation of osteopontin in response to mechanical stress. J. Bone Miner. Res. 21, 956\u2013964. https:\/\/doi.org\/10.1359\/jbmr.060315 (2006).","journal-title":"J. Bone Miner. Res."},{"key":"52566_CR86","doi-asserted-by":"publisher","first-page":"1892","DOI":"10.1093\/jn\/133.6.1892","volume":"133","author":"H Chiba","year":"2003","unstructured":"Chiba, H. et al. Hesperidin, a citrus flavonoid, inhibits bone loss and decreases serum and hepatic lipids in ovariectomized mice. J. Nutr. 133, 1892\u20131897. https:\/\/doi.org\/10.1093\/jn\/133.6.1892 (2003).","journal-title":"J. Nutr."},{"key":"52566_CR87","doi-asserted-by":"publisher","first-page":"369","DOI":"10.1016\/j.mce.2016.09.026","volume":"439","author":"Z Tan","year":"2017","unstructured":"Tan, Z. et al. Neohesperidin suppresses osteoclast differentiation, bone resorption and ovariectomised-induced osteoporosis in mice. Mol. Cell Endocrinol. 439, 369\u2013378. https:\/\/doi.org\/10.1016\/j.mce.2016.09.026 (2017).","journal-title":"Mol. Cell Endocrinol."},{"key":"52566_CR88","doi-asserted-by":"publisher","first-page":"5419","DOI":"10.2147\/dddt.S255276","volume":"14","author":"S Yuan","year":"2020","unstructured":"Yuan, S., Zhang, C., Zhu, Y. & Wang, B. Neohesperidin ameliorates steroid-induced osteonecrosis of the femoral head by inhibiting the histone modification of lncRNA HOTAIR. Drug Des. Dev. Ther. 14, 5419\u20135430. https:\/\/doi.org\/10.2147\/dddt.S255276 (2020).","journal-title":"Drug Des. Dev. Ther."},{"key":"52566_CR89","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.i17","volume":"352","author":"ML Bertoia","year":"2016","unstructured":"Bertoia, M. L. et al. Dietary flavonoid intake and weight maintenance: three prospective cohorts of 124,086 US men and women followed for up to 24 years. BMJ 352, i17. https:\/\/doi.org\/10.1136\/bmj.i17 (2016).","journal-title":"BMJ"},{"key":"52566_CR90","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2020.105291","volume":"164","author":"CC Chen","year":"2021","unstructured":"Chen, C. C., Kuo, C. H., Leu, Y. L. & Wang, S. H. Corylin reduces obesity and insulin resistance and promotes adipose tissue browning through SIRT-1 and \u03b23-AR activation. Pharmacol. Res. 164, 105291. https:\/\/doi.org\/10.1016\/j.phrs.2020.105291 (2021).","journal-title":"Pharmacol. Res."}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-024-52566-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-024-52566-7","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-024-52566-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,1,31]],"date-time":"2024-01-31T10:12:00Z","timestamp":1706695920000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-024-52566-7"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,1,31]]},"references-count":90,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2024,12]]}},"alternative-id":["52566"],"URL":"https:\/\/doi.org\/10.1038\/s41598-024-52566-7","relation":{"has-preprint":[{"id-type":"doi","id":"10.21203\/rs.3.rs-3353141\/v1","asserted-by":"object"}]},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,1,31]]},"assertion":[{"value":"13 September 2023","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"20 January 2024","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"31 January 2024","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"2602"}}