{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T04:24:47Z","timestamp":1787804687990,"version":"build-2784847793"},"reference-count":49,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2022,10,5]],"date-time":"2022-10-05T00:00:00Z","timestamp":1664928000000},"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":["81571010"],"award-info":[{"award-number":["81571010"]}],"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>Objectives<\/jats:title><jats:p>To investigate the effects of cellular communication network factor 1 (CCN1), a critical matricellular protein, on alveolar bone regeneration, and to elucidate the underlying molecular mechanism.<\/jats:p><\/jats:sec><jats:sec><jats:title>Background<\/jats:title><jats:p>In the process of orthodontic tooth movement, bone deposition on the tension side of human periodontal ligament stem cells (hPDLSCs) ensured high efficiency and long\u2010term stability of the treatment. The matricellular protein CCN1 is responsive to mechanical stimulation, exhibiting important tasks in bone homoeostasis. However, the role and mechanism of CCN1 on alveolar bone remodeling of hPDLSCs remains unclear.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The expression and distribution of CCN1 in rat periodontal ligament were detected by immunofluorescence staining and immunohistochemical staining. ELISA verified the secretion of CCN1 triggered by stretch loading. To examine the mineralization ability of hPDLSCs induced by CCN1, Western blotting, qRT\u2010PCR, ARS, and ALP staining were performed. CCK\u20108 and cell migration assay were performed to detect the cell proliferation rate and the wound healing. PI3K\/Akt, MAPK, and autophagy activation were examined via Western blotting and immunofluorescence.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Mechanical stimuli induced the release of CCN1 into extracellular environment by hPDLSCs. Knockdown of CCN1 attenuated the osteogenesis of hPDLSCs while rhCCN1 enhanced the expression of Runx2, Col 1, ALPL, and promoted the mineralization nodule formation. CCN1 activated PI3K\/Akt and ERK signaling, and blockage of PI3K\/Akt signaling reversed the accelerated cell migration triggered by CCN1. The enhanced osteogenesis induced by CCN1 was abolished by ERK signaling inhibitor PD98059 or autophagy inhibitor 3\u2010MA. Further investigation demonstrated PD98059 abrogated the activation of autophagy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>This study demonstrated that CCN1 promotes osteogenesis in hPDLSCs via autophagy and MAPK\/ERK pathway.<\/jats:p><\/jats:sec>","DOI":"10.1111\/jre.13054","type":"journal-article","created":{"date-parts":[[2022,10,6]],"date-time":"2022-10-06T04:49:11Z","timestamp":1665031751000},"page":"1169-1182","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Cellular\u00a0communication network factor 1 interlinks autophagy and <scp>ERK<\/scp> signaling to promote osteogenesis of periodontal ligament stem cells"],"prefix":"10.1111","volume":"57","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2488-814X","authenticated-orcid":false,"given":"Zixuan","family":"Li","sequence":"first","affiliation":[{"name":"Department of Orthodontics, School and Hospital of Stomatology, Cheeloo College of Medicine Shandong University &amp; Shandong Key Laboratory of Oral Tissue Regeneration &amp; Shandong Engineering Laboratory for Dental Materials and Oral Tissue Regeneration  Jinan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zuping","family":"Wu","sequence":"additional","affiliation":[{"name":"Stomatology Hospital, School of Stomatology, Zhejiang University School of Medicine, Clinical Research Center for Oral Diseases of Zhejiang Province, Key Laboratory of Oral Biomedical Research of Zhejiang Province Cancer Center of Zhejiang University  Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xun","family":"Xi","sequence":"additional","affiliation":[{"name":"Department of Orthodontics, School and Hospital of Stomatology, Cheeloo College of Medicine Shandong University &amp; Shandong Key Laboratory of Oral Tissue Regeneration &amp; Shandong Engineering Laboratory for Dental Materials and Oral Tissue Regeneration  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