{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T23:40:38Z","timestamp":1787614838432,"version":"build-2736575974"},"reference-count":50,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2019,9,21]],"date-time":"2019-09-21T00:00:00Z","timestamp":1569024000000},"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":["81570981"],"award-info":[{"award-number":["81570981"]}],"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":["31600788"],"award-info":[{"award-number":["31600788"]}],"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":[[2020,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background and Objectives<\/jats:title>\n                    <jats:p>As a chronic infectious disease, periodontitis could lead to tooth and bone loss. Low\u2010intensity pulsed ultrasound (LIPUS) is a safe, noninvasive treatment method to effectively inhibit inflammation and promote bone differentiation. However, the application of LIPUS in curing periodontitis is still rare. Our study aimed to explore the ability of LIPUS to inhibit inflammatory factors and promote the osteogenic differentiation capacity of human periodontal ligament cells (hPDLCs), and its underlying mechanism.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Material and Methods<\/jats:title>\n                    <jats:p>\n                      Human periodontal ligament cells were obtained and cultured from the premolar tissue samples for experiments. First, hPDLCs were treated for 24 hours using lipopolysaccharide (LPS) and then exposed to LIPUS (10 mW\/cm\n                      <jats:sup>2<\/jats:sup>\n                      , 30 mW\/cm\n                      <jats:sup>2<\/jats:sup>\n                      , 60 mW\/cm\n                      <jats:sup>2<\/jats:sup>\n                      , and 90 mW\/cm\n                      <jats:sup>2<\/jats:sup>\n                      ) to determine the appropriate intensity to inhibit expression of the inflammatory factors interleukin\u20106 (IL\u20106) and interleukin\u20108 (IL\u20108) expression. The expression of IL\u20106 and IL\u20108 was detected by real\u2010time PCR and enzyme\u2010linked immunosorbent assay. The safety of the most appropriate intensity of LIPUS was tested by a cell counting kit 8 test and an apoptosis assay. Then, LPS\u2010induced hPDLCs were treated in osteogenic medium for 7\u201021 days with or without LIPUS (90 mW\/cm\n                      <jats:sup>2<\/jats:sup>\n                      , 30 min\/d) stimulation. The osteogenic genes RUNX2, OPN, OSX, and OCN were measured by real\u2010time PCR. Additionally, osteogenic differentiation capacity was determined using alkaline phosphatase (ALP) staining, ALP activity analysis, and Alizarin red staining. The activity of the nuclear factor\u2010kappa B (NF\u2010\u03baB) signaling pathway was determined by western blotting, real\u2010time PCR, immunofluorescence, and pathway blockade assays.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Lipopolysaccharide significantly upregulated the production and gene expression of IL\u20106 and IL\u20108, while LIPUS stimulation significantly inhibited IL\u20106 and IL\u20108 expression in an intensity\u2010dependent manner. LIPUS (90 mW\/cm\n                      <jats:sup>2<\/jats:sup>\n                      ) was chosen as the most appropriate intensity, and there was no detrimental influence on cell proliferation and status with or without osteogenic medium. In addition, consecutive stimulation with LIPUS (90 mW\/cm\n                      <jats:sup>2<\/jats:sup>\n                      ) for 30 min\/d for 7 days could also inhibit IL\u20106 and IL\u20108 gene expression, upregulate the expression of the osteogenesis\u2010related genes RUNX2, OPN, OSX, and OCN, and promote osteogenic differentiation capacity in osteogenic medium in inflamed hPDLCs. The NF\u2010\u03baB signaling pathway was inhibited with LIPUS (90 mW\/cm\n                      <jats:sup>2<\/jats:sup>\n                      ) via inhibition of the phosphorylation of I\u03baB\u03b1 and the translocation of p65 into the nucleus in inflamed hPDLCs. Additional investigations of the NF\u2010\u03baB inhibitor, BAY 11\u20107082, revealed that LIPUS (90 mW\/cm\n                      <jats:sup>2<\/jats:sup>\n                      ) acted similarly to BAY 11\u20107802 to inhibit the NF\u2010\u03baB signaling pathway and increase osteogenesis\u2010related genes and promote the osteogenic differentiation capacity of inflamed hPDLCs.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      Low\u2010intensity pulsed ultrasound (90 mW\/cm\n                      <jats:sup>2<\/jats:sup>\n                      ) stimulation could be a safe method to inhibit IL\u20106 and IL\u20108 in hPDLCs by inhibiting the NF\u2010\u03baB signaling pathway. The effect of LIPUS (90 mW\/cm\n                      <jats:sup>2<\/jats:sup>\n                      ) and BAY 11\u20107082 on LPS\u2010induced inflammation demonstrated that both of these agents were capable of promoting osteogenesis\u2010related gene expression and osteogenic differentiation in hPDLCs, suggesting that the effect of LIPUS on the promotion of osteogenic activity could be mediated in part through its ability to inhibit the NF\u2010\u03baB signal pathway. Hence, LIPUS could be a potential therapeutic method to cure periodontitis.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/jre.12696","type":"journal-article","created":{"date-parts":[[2019,9,21]],"date-time":"2019-09-21T04:20:40Z","timestamp":1569039640000},"page":"125-140","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":58,"title":["LIPUS inhibited the expression of inflammatory factors and promoted the osteogenic differentiation capacity of hPDLCs by inhibiting the NF\u2010\u03baB signaling pathway"],"prefix":"10.1111","volume":"55","author":[{"given":"Shan","family":"Liu","sequence":"first","affiliation":[{"name":"Chongqing Key Laboratory of Oral Diseases and Biomedical Sciences Chongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher Education College of Stomatology Chongqing Medical University Chongqing 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