{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T03:16:11Z","timestamp":1792984571424,"version":"4.5.0"},"reference-count":34,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2022,2,3]],"date-time":"2022-02-03T00:00:00Z","timestamp":1643846400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["aap.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Periodontology"],"published-print":{"date-parts":[[2022,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Periodontitis could lead to periodontal destruction such as the loss of alveolar bone. The issue that how to achieve the regeneration of alveolar bone and periodontal tissues under the inflammatory environment needs to be solved urgently. Bone morphogenetic protein 9 (BMP9) is one of the most potent osteoinductive BMPs and induces osteogenic differentiation of mesenchymal stem cells. The aim of this study is to explore the possible effect of BMP9 on the osteogenic differentiation of inflammatory periodontal ligament stem cells (PDLSCs).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Human PDLSCs were cultured in osteoinductive medium with 1\u00a0\u03bcg\/mL lipopolysaccharide <jats:italic>Porphyromonas gingivitis<\/jats:italic> (LPS\u2010PG). Adenoviral vector expressing system was used to overexpress target genes. In vitro expression of osteogenic markers was assessed by quantitative reverse transcription polymerase chain reaction, Western blotting, alkaline phosphatase assay, and alizarin red staining. Subcutaneous implantation nude mice models were used to evaluate the effects of BMP9 on PDLSCs in vivo. Microcomputed tomography, hematoxylin &amp; eosin staining, and trichrome staining were performed to assess ectopic bone formation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In the LPS\u2010PG induced inflammatory environment, BMP9 promoted osteogenic differentiation of PDLSCs, but upregulated the expression of inflammatory markers (<jats:italic>P<\/jats:italic>\u00a0&gt; 0.05); NEL\u2010like protein 1 (NELL1) downregulated the expression of inflammation genes in PDLSCs induced by BMP9, while augmenting BMP9\u2010induced osteogenesis of the cells both in vitro and in vivo. In the above process, the MAPK\/p38\/ERK signaling pathway was triggered by NELL1.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The combination use of BMP9 and NELL1 might have the potential to promote the regeneration of alveolar bone in periodontitis.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jper.20-0517","type":"journal-article","created":{"date-parts":[[2021,10,15]],"date-time":"2021-10-15T22:08:29Z","timestamp":1634335709000},"page":"977-987","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["NELL1 augments osteogenesis and inhibits inflammation of human periodontal ligament stem cells induced by BMP9"],"prefix":"10.1002","volume":"93","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1243-9654","authenticated-orcid":false,"given":"Liu","family":"Wang","sequence":"first","affiliation":[{"name":"State Key Laboratory of Oral Diseases &amp; National Clinical Research Center of Oral Disease, West China Hospital of Stomatology Sichuan University  Chengdu Sichuan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6752-4878","authenticated-orcid":false,"given":"Xiangfen","family":"Li","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Oral Diseases &amp; National Clinical Research Center of Oral Disease, West China Hospital of Stomatology Sichuan University  Chengdu Sichuan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1566-8893","authenticated-orcid":false,"given":"Yao","family":"Song","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Oral Diseases &amp; National Clinical Research Center of Oral Disease, West China Hospital of Stomatology Sichuan University  Chengdu Sichuan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lan","family":"Zhang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Oral Diseases &amp; National Clinical Research Center of Oral Disease, West China Hospital of Stomatology Sichuan University  Chengdu Sichuan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ling","family":"Ye","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Oral Diseases &amp; National Clinical Research Center of Oral Disease, West China Hospital of Stomatology Sichuan University  Chengdu Sichuan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuedong","family":"Zhou","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Oral Diseases &amp; National Clinical Research Center of Oral Disease, West China Hospital of Stomatology Sichuan University  Chengdu Sichuan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5241-2013","authenticated-orcid":false,"given":"Dongzhe","family":"Song","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Oral Diseases &amp; National Clinical Research Center of Oral Disease, West China Hospital of Stomatology Sichuan University  Chengdu Sichuan China"},{"name":"Department of Operative Dentistry and Endodontics, West China Hospital of Stomatology Sichuan University  Chengdu Sichuan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0779-5729","authenticated-orcid":false,"given":"Dingming","family":"Huang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Oral Diseases &amp; National Clinical Research Center of Oral Disease, West China Hospital of Stomatology Sichuan University  Chengdu Sichuan China"},{"name":"Department of Operative Dentistry and Endodontics, West China Hospital of Stomatology Sichuan University  Chengdu Sichuan China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,2,3]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41368-019-0064-z"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri3785"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/prd.12221"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1155\/2015\/615486"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(04)16627-0"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gendis.2019.07.003"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/boneres.2016.9"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gendis.2019.03.008"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells8121579"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1089\/scd.2018.0230"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-08278-4"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1042\/BST20200376"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.3957"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/jcmm.13193"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0169123"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.joen.2016.08.013"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0024638"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbm.a.36359"},{"key":"e_1_2_8_20_1","doi-asserted-by":"crossref","unstructured":"LiP LiY ZhuL et\u00a0al.Targeting secreted cytokine BMP9 gates the attenuation of hepatic fibrosis.2018;1864:709\u2010720.","DOI":"10.1016\/j.bbadis.2017.12.008"},{"key":"e_1_2_8_21_1","doi-asserted-by":"crossref","unstructured":"SLA CGM AC et\u00a0al.Bone morphogenetic protein 9 enhances lipopolysaccharide\u2010induced leukocyte recruitment to the vascular endothelium.2016;197:3302\u20103314.","DOI":"10.4049\/jimmunol.1601219"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1159\/000456885"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2019.119541"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gendis.2017.07.006"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms8362"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1359\/jbmr.061012"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.267"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajpath.2016.12.026"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellsig.2010.10.003"},{"key":"e_1_2_8_30_1","first-page":"1","article-title":"BMP9 signaling in stem cell differentiation and osteogenesis","volume":"2","author":"Lamplot JD","year":"2013","journal-title":"Am J Stem Cells"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.7150\/ijms.8473"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2020.584798"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1111\/cpr.12957"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1042\/CS20180679"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10753-018-0933-1"}],"container-title":["Journal of Periodontology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/JPER.20-0517","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/JPER.20-0517","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/aap.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/JPER.20-0517","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,19]],"date-time":"2025-10-19T11:57:35Z","timestamp":1760875055000},"score":1,"resource":{"primary":{"URL":"https:\/\/aap.onlinelibrary.wiley.com\/doi\/10.1002\/JPER.20-0517"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,2,3]]},"references-count":34,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2022,7]]}},"alternative-id":["10.1002\/JPER.20-0517"],"URL":"https:\/\/doi.org\/10.1002\/jper.20-0517","archive":["Portico"],"relation":{},"ISSN":["0022-3492","1943-3670"],"issn-type":[{"value":"0022-3492","type":"print"},{"value":"1943-3670","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,2,3]]},"assertion":[{"value":"2020-08-03","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-09-26","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-02-03","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}