{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T22:38:41Z","timestamp":1790116721728,"version":"4.0.1"},"reference-count":62,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2022,10,12]],"date-time":"2022-10-12T00:00:00Z","timestamp":1665532800000},"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":["82071168"],"award-info":[{"award-number":["82071168"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Periodontal Research"],"published-print":{"date-parts":[[2022,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background and objective<\/jats:title><jats:p>Hydroxyapatite scaffolds with different morphologies have been widely used in bone tissue engineering. Moreover, microRNAs (miRNAs) have been proven to be extensively involved in regulating bone regeneration. We developed grooved porous hydroxyapatite (HAG) scaffolds with good osteogenic efficiency. However, little is known about the role of miRNAs in HAG scaffold\u2010mediated promotion of bone regeneration. The objective of this study was to reveal the mechanism from the perspective of differential miRNA expression.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Scanning electron microscopy (SEM) was used to perform the coculture of cells and scaffolds. The miRNA profiles were generated by a microarray assay. A synthetic miR\u2010129\u20105p mimic and inhibitor were used for overexpression or inhibition. The expression of osteogenic marker mRNAs and proteins was detected by quantitative real\u2010time PCR (qRT\u2013PCR), Western blotting, and immunofluorescence. An ALP activity kit and alizarin red staining (ARS) were used to measure ALP activity and mineral deposition formation. Cell migration ability was examined by wound healing and transwell assays. Protein kinase A (PKA) activity was measured by enzyme\u2010linked immunosorbent assay (ELISA) after miR\u2010129\u20105p transfection. Target genes were identified by a dual\u2010luciferase reporter assay. H89 preculture evaluated the cross talk between miR\u2010129\u20105p and PKA activity. Heterotopic implantation models, hematoxylin\u2013eosin (HE), immunohistochemistry staining, and micro\u2010CT were used to evaluate miR\u2010129\u20105p osteogenesis in vivo.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>miRNAs were differentially expressed during osteogenic differentiation induced by HAG in vitro and in vivo. miR\u2010129\u20105p was the only highly expressed miRNA both in vitro and in vivo. miR\u2010129\u20105p overexpression promoted osteoblast differentiation and cell migration, while its inhibition weakened the effect of HAG. Moreover, miR\u2010129\u20105p activated PKA to regulate the phosphorylation of \u03b2\u2010catenin and cAMP\u2010response element binding protein (CREB) by inhibiting cAMP\u2010dependent protein kinase inhibitor alpha (Pkia). H89 prevented the effects of miR\u2010129\u20105p on osteogenic differentiation and cell migration. HE, immunohistochemistry staining and micro\u2010CT results showed that miR\u2010129\u20105p promoted in vivo osteogenesis of the HAG scaffold.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The HAG scaffold activates Pka by upregulating miR\u2010129\u20105p and inhibiting Pkia, resulting in CREB\u2010dependent transcriptional activation and accumulation of \u03b2\u2010catenin and promoting osteogenic marker expression.<\/jats:p><\/jats:sec>","DOI":"10.1111\/jre.13060","type":"journal-article","created":{"date-parts":[[2022,10,12]],"date-time":"2022-10-12T11:23:34Z","timestamp":1665573814000},"page":"1238-1255","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["A grooved porous hydroxyapatite scaffold induces osteogenic differentiation via regulation of <scp>PKA<\/scp> activity by upregulating <scp>miR<\/scp>\u2010129\u20105p expression"],"prefix":"10.1111","volume":"57","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1369-2128","authenticated-orcid":false,"given":"Li","family":"Deng","sequence":"first","affiliation":[{"name":"Stomatology Department, Sichuan Provincial People's Hospital, School of Medicine University of Electronic Science and Technology of China  Chengdu China"},{"name":"Institute of Tissue Engineering and Stem Cells Nanchong Central Hospital, The Second Clinical College of North Sichuan Medical College  Nanchong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinlun","family":"Li","sequence":"additional","affiliation":[{"name":"Stomatology Department Sichuan Provincial People's Hospital  Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaohua","family":"Ren","sequence":"additional","affiliation":[{"name":"Stomatology Department, Sichuan Provincial People's Hospital, School of Medicine University of Electronic Science and Technology of China  Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuang","family":"Lai","sequence":"additional","affiliation":[{"name":"Stomatology Department, Sichuan Provincial People's Hospital, School of Medicine University of Electronic Science and Technology of China  Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yushu","family":"Zhu","sequence":"additional","affiliation":[{"name":"Stomatology Department Sichuan Provincial People's Hospital  Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Li","sequence":"additional","affiliation":[{"name":"Stomatology Department Sichuan Provincial People's Hospital  Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao","family":"Huang","sequence":"additional","affiliation":[{"name":"<!--Query ID=\"q2\" Text=\"AUTHOR: Please check all the affiliations and correspondence information are OK as typeset.\"-->Key Laboratory of Advanced Technologies of Materials (Ministry of Education), School of Materials Science and Engineering Southwest Jiaotong University  Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yandong","family":"Mu","sequence":"additional","affiliation":[{"name":"Stomatology Department, Sichuan Provincial People's Hospital, School of Medicine University of Electronic Science and Technology of China  Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,10,12]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/boneres.2017.59"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0142-9612(00)00102-2"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.actbio.2011.03.019"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.actbio.2013.05.026"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrn2739"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.82"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/bies.200800212"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cytogfr.2005.02.003"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.4161\/cc.7.14.6257"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.msec.2020.110641"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1039\/C7TB01970J"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1093\/rb\/rbw031"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ceramint.2018.08.249"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrendo.2011.234"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2010.03.010"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2011.01.014"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0707900105"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ydbio.2010.01.008"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M809787200"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1089\/dna.2021.0850"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1210\/mend-5-9-1246"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M508778200"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.25.20.9063-9072.2005"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0711190105"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.24171"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms19123916"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.msec.2018.08.023"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2019.108649"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1089\/ten.tea.2009.0337"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.2001.81.4.1415"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1177\/0300060520978015"},{"issue":"5","key":"e_1_2_9_33_1","first-page":"4558","article-title":"miR 483 3p regulates osteogenic differentiation of bone marrow mesenchymal stem cells by targeting STAT1","volume":"20","author":"Xiao Y","year":"2019","journal-title":"Mol Med Rep"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1080\/1354750X.2016.1204000"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202001334"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells8070742"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1155\/2021\/7435605"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2020.600641"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2007.03.017"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.RA118.004102"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1002\/mabi.200400026"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0142-9612(03)00030-9"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1002\/bit.260420606"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/S8756-3282(00)00424-5"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0962-8924(03)00105-3"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0962-8924(01)02152-3"},{"key":"e_1_2_9_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1357-2725(99)00043-6"},{"key":"e_1_2_9_48_1","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/cdf399"},{"key":"e_1_2_9_49_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsami.7b18289"},{"key":"e_1_2_9_50_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2007.11.028"},{"key":"e_1_2_9_51_1","first-page":"3","article-title":"Calcium and phosphate homeostasis: concerted interplay of new regulators","volume":"34","author":"Civitelli R","year":"2011","journal-title":"J Endocrinol Invest"},{"key":"e_1_2_9_52_1","doi-asserted-by":"publisher","DOI":"10.1038\/366575a0"},{"key":"e_1_2_9_53_1","doi-asserted-by":"publisher","DOI":"10.4161\/org.19808"},{"key":"e_1_2_9_54_1","doi-asserted-by":"publisher","DOI":"10.1038\/emboj.2012.49"},{"key":"e_1_2_9_55_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.29681"},{"key":"e_1_2_9_56_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.13779"},{"key":"e_1_2_9_57_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00251.2015"},{"key":"e_1_2_9_58_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms20215341"},{"key":"e_1_2_9_59_1","doi-asserted-by":"publisher","DOI":"10.7150\/thno.42640"},{"key":"e_1_2_9_60_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2014.04.048"},{"key":"e_1_2_9_61_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.msec.2019.110128"},{"key":"e_1_2_9_62_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1016758108"},{"key":"e_1_2_9_63_1","doi-asserted-by":"publisher","DOI":"10.1002\/stem.1615"}],"container-title":["Journal of Periodontal Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jre.13060","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/jre.13060","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jre.13060","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,21]],"date-time":"2023-08-21T18:56:21Z","timestamp":1692644181000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/jre.13060"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,10,12]]},"references-count":62,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2022,12]]}},"alternative-id":["10.1111\/jre.13060"],"URL":"https:\/\/doi.org\/10.1111\/jre.13060","archive":["Portico"],"relation":{},"ISSN":["0022-3484","1600-0765"],"issn-type":[{"value":"0022-3484","type":"print"},{"value":"1600-0765","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,10,12]]},"assertion":[{"value":"2022-06-03","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-09-27","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-10-12","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}