{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,21]],"date-time":"2026-02-21T04:51:43Z","timestamp":1771649503044,"version":"3.50.1"},"reference-count":37,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2019,12,19]],"date-time":"2019-12-19T00:00:00Z","timestamp":1576713600000},"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":["81702684"],"award-info":[{"award-number":["81702684"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81771076"],"award-info":[{"award-number":["81771076"]}],"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":[[2020,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>To investigate the molecular mechanism of Progranulin (PGRN) in promoting osteogenic differentiation of human periodontal ligament stem cells (hPDLSCs) in inflammatory environment.<\/jats:p><\/jats:sec><jats:sec><jats:title>Background<\/jats:title><jats:p>Progranulin is an antagonist of tumor necrosis factor (TNF) receptors (TNFRs) and is known to promote inflammatory periodontal bone defect regeneration.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>TNFR1\u2010 and TNFR2\u2010silenced hPDLSCs designed as hPDLSCs\u2010sh\u2010TNFR1 and hPDLSCs\u2010sh\u2010TNFR2 were cultured with osteoinductive medium containing TNF\u2010\u03b1 and (or) PGRN. Immunofluorescence, quantitative real\u2010time PCR, and western blot were used to, respectively, detect expressions of TNFR1\\TNFR2 and osteogenic differentiation markers as well as phosphorylation level in NF\u2010\u03baB\\MAPK\u2010related pathways.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Immunofluorescence and real\u2010time PCR showed that TNFR1 and TNFR2 positively expressed in hPDLSCs. TNF\u2010\u03b1 stimulation could significantly decrease the expressions of ALP and RUNX2 in hPDLSCs, whereas PGRN treatment could significantly enhance their expressions, and reverse TNF\u2010\u03b1\u2010mediated expression suppression of ALP and RUNX2 in hPDLSCs. In hPDLSCs\u2010sh\u2010TNFR1, TNF\u2010\u03b1 mediated osteogenic inhibition decreased, but both TNF\u2010\u03b1\u00a0+\u00a0PGRN and alone PGRN significantly promoted expression of ALP and RUNX2. PGRN significantly enhanced expression of P\u2010ERK1\/2 and P\u2010JNK, while corresponding inhibitors eliminated PGRN\u2010stimulated osteogenic differentiation. In hPDLSCs\u2010sh\u2010TNFR2, no significant difference existed in osteogenic markers and P\u2010JNK expression between the PGRN group and the control group. However, PGRN still activated P\u2010ERK1\/2 expression. Besides, PGRN antagonized TNF\u2010\u03b1\u2010enhanced NF\u2010\u03baB P65 expression.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Progranulin promotes osteogenic differentiation of hPDLSCs via TNFR1 to inhibit TNF\u2010\u03b1\u2010sensitized NF\u2010\u03baB and via TNFR2 to activate JNK signaling. The mechanism by which PGRN activates ERK signaling remains to be explored.<\/jats:p><\/jats:sec>","DOI":"10.1111\/jre.12720","type":"journal-article","created":{"date-parts":[[2019,12,19]],"date-time":"2019-12-19T12:31:50Z","timestamp":1576758710000},"page":"363-373","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["Progranulin promotes osteogenic differentiation of human periodontal ligament stem cells via tumor necrosis factor receptors to inhibit TNF\u2010\u03b1 sensitized NF\u2010kB and activate ERK\/JNK signaling"],"prefix":"10.1111","volume":"55","author":[{"given":"Jing","family":"Chen","sequence":"first","affiliation":[{"name":"Shandong Provincial Key Laboratory of Oral Tissue Regeneration School of Stomatology Shandong University Jinan China"},{"name":"Department of Periodontology School of Stomatology Shandong University Jinan 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