{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,29]],"date-time":"2025-09-29T20:27:56Z","timestamp":1759177676740,"version":"3.37.3"},"reference-count":40,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2020,4,23]],"date-time":"2020-04-23T00:00:00Z","timestamp":1587600000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["31771331","31971108","81741016"],"award-info":[{"award-number":["31771331","31971108","81741016"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003453","name":"Natural Science Foundation of Guangdong Province","doi-asserted-by":"publisher","award":["2020A1515010209"],"award-info":[{"award-number":["2020A1515010209"]}],"id":[{"id":"10.13039\/501100003453","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal Cellular Physiology"],"published-print":{"date-parts":[[2020,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Folic acid (FA) is routinely supplemented in the food of pregnant women or women planning a pregnancy, but whether FA exerts a positive effect on preventing fetal bone malformation remains obscure. In this study, we first exposed chick embryos with different concentrations of FA (1\u201310,000\u2009pmol\/egg) and studied vertebral mineralization and ossification through alcian blue and alizarin red as well as hematoxylin and eosin staining. Morphological measurements of the thoracic vertebral bodies demonstrated that 100\u2009pmol\/egg FA exhibited the tendency of shortening the growth plate, extended the ossification center, and increased the amount of Type I collagen. Second, we suggested that FA treatment promotes osteogenesis by demonstrating increased RUNX family transcription factor 2 (Runx2) and Osterix expressions in MC3T3\u2010E1 and ATDC5 cells. Transforming growth factor\u2010\u03b2 (TGF\u2010\u03b2) signaling was also upregulated by FA exposure, and addition of smad2\/3 small interfering RNA knocks down FA\u2010induced increased p\u2010smad2\/3, Runx2, and Osterix expression in vitro during chondrogenesis induction. Third, we employed dexamethasone (Dex), exposed chick embryos as an animal model of skeletal developmental retardation, to explore whether FA could rescue the loss of embryonic bone mass. Micro\u2010computed tomography imaging showed that the addition of FA improved the reduction of bone mass in our model. Histological analysis of the vertebral bodies revealed that FA dramatically improved the delayed turnover of the zones of growth plate caused by Dex exposure. Immunofluorescence on the chick embryonic vertebrae and chondrocytes showed that FA supplementation upregulated the expression of TGF\u2010\u03b21, p\u2010smad2\/3, and improved Runx2 as well as Osterix expression in the Dex\u2009+\u2009FA group compared with the Dex group. Lastly, we found that supplementation with TGF\u2010\u03b21 (1\u2009ng\/egg) rescued bone mass loss caused by Dex as was also seen in FA exposure. Taken together these results, our data revealed that FA supplementation was able to rescue Dex exposure\u2010induced inhibitive osteogenesis through targeting on the TGF\u2010\u03b2 signaling pathway.<\/jats:p>","DOI":"10.1002\/jcp.29707","type":"journal-article","created":{"date-parts":[[2020,4,23]],"date-time":"2020-04-23T15:45:52Z","timestamp":1587656752000},"page":"8626-8639","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Folic acid rescues corticosteroid\u2010induced vertebral malformations in chick embryos through targeting TGF\u2010\u03b2 signaling"],"prefix":"10.1002","volume":"235","author":[{"given":"Hongmei","family":"Cai","sequence":"first","affiliation":[{"name":"Division of Histology and Embryology, Joint Laboratory for Embryonic, Development and Prenatal Medicine, Medical College Jinan University  Guangzhou China"},{"name":"Key Laboratory for Regenerative Medicine of the Ministry of Education Jinan University  Guangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Li","family":"Lin","sequence":"additional","affiliation":[{"name":"Division of Histology and Embryology, Joint Laboratory for Embryonic, Development and Prenatal Medicine, Medical College Jinan University  Guangzhou China"},{"name":"Key Laboratory for Regenerative Medicine of the Ministry of Education Jinan University  Guangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guang","family":"Wang","sequence":"additional","affiliation":[{"name":"Division of Histology and Embryology, Joint Laboratory for Embryonic, Development and Prenatal Medicine, Medical College Jinan University  Guangzhou China"},{"name":"Key Laboratory for Regenerative Medicine of the Ministry of Education Jinan University  Guangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zachary","family":"Berman","sequence":"additional","affiliation":[{"name":"Department of Radiology University of California San Diego  San Diego California"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2537-5752","authenticated-orcid":false,"given":"Xuesong","family":"Yang","sequence":"additional","affiliation":[{"name":"Division of Histology and Embryology, Joint Laboratory for Embryonic, Development and Prenatal Medicine, Medical College Jinan University  Guangzhou China"},{"name":"Key Laboratory for Regenerative Medicine of the Ministry of Education Jinan University  Guangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xin","family":"Cheng","sequence":"additional","affiliation":[{"name":"Division of Histology and Embryology, Joint Laboratory for Embryonic, Development and Prenatal Medicine, Medical College Jinan University  Guangzhou China"},{"name":"Key Laboratory for Regenerative Medicine of the Ministry of Education Jinan University  Guangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2020,4,23]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ydbio.2006.06.002"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ydbio.2004.08.027"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1093\/ije\/dyq028"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejogrb.2018.12.025"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.22203\/eCM.v028a19"},{"key":"e_1_2_8_7_1","first-page":"41","article-title":"3 Patterning and differentiation of the vertebrate spine","volume":"53","author":"Chal J.","year":"2009","journal-title":"Cold Spring Harbor Monograph Archive"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.7150\/ijbs.2929"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.toxlet.2018.01.008"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.taap.2014.09.014"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijgo.12746"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.reprotox.2018.05.004"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00774\u2010010\u20100205\u20100"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1677\/joe.1.05962"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.febslet.2011.03.034"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.3109\/10520299509108199"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00418\u2010018\u20101640\u20106"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1205937"},{"volume-title":"UpToDate","year":"2018","author":"Lee M. \u2010J.","key":"e_1_2_8_19_1"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmjopen-2018-028843"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ydbio.2009.06.002"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.17458\/per.vol16.2018.mcpa.dexamethasone"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00418\u2010015\u20101334\u20102"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncb3098"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2010.05.005"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474\u20104422(06)70598\u20101"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.124.13.2659"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1002\/jmor.1052130305"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pbj.2017.05.006"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.96.21.11776"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/bonekey.2015.80"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1177\/1078155210366492"},{"volume-title":"Folic acid supplementation: An evidence review for the US preventive services task force","year":"2017","author":"Viswanathan M.","key":"e_1_2_8_33_1"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1002\/bdrc.21058"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbi.2004.09.006"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1038\/boneres.2016.9"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.21274"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.28157"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.139550"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.13506"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0912855107"}],"container-title":["Journal of Cellular Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fjcp.29707","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jcp.29707","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/jcp.29707","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jcp.29707","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,11,20]],"date-time":"2024-11-20T17:02:30Z","timestamp":1732122150000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jcp.29707"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,4,23]]},"references-count":40,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2020,11]]}},"alternative-id":["10.1002\/jcp.29707"],"URL":"https:\/\/doi.org\/10.1002\/jcp.29707","archive":["Portico"],"relation":{},"ISSN":["0021-9541","1097-4652"],"issn-type":[{"type":"print","value":"0021-9541"},{"type":"electronic","value":"1097-4652"}],"subject":[],"published":{"date-parts":[[2020,4,23]]},"assertion":[{"value":"2020-01-07","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-04-02","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-04-23","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}