{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T20:09:34Z","timestamp":1782331774696,"version":"3.54.5"},"reference-count":48,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2019,4,21]],"date-time":"2019-04-21T00:00:00Z","timestamp":1555804800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Cellular Biochemistry"],"published-print":{"date-parts":[[2019,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Periodontal ligament fibroblasts (PDLFs) have osteogenic capacity, producing bone matrix proteins. Application of bone morphogenic proteins (BMPs) to PDLFs is a promising approach for periodontal regeneration. However, in chronic bone metabolic disorders, such as periodontitis, proper control of accompanying inflammation is essential for optimizing the effects of BMPs on PDLFs. We have previously shown that low\u2010intensity pulsed ultrasound (LIPUS), a medical technology that induces mechanical stress using sound waves, significantly promotes osteogenesis in mesenchymal stem cells. Here, we demonstrate that LIPUS promotes the BMP9\u2010induced osteogenic differentiation of PDLFs. In contrast, BMP2\u2010induced osteogenic differentiation was not altered by LIPUS, probably due to the LIPUS\u2010induced secretion of Noggin, a BMP2 antagonist, from PDLFs. To examine if LIPUS affects inflammatory responses of PDLFs to\u00a0lipopolysaccharide (LPS) derived from <jats:italic>Porphyromonas gingivalis<\/jats:italic> (LPS\u2010PG), we also simultaneously treated PDLFs with LIPUS and LPS\u2010PG. Treatment with LIPUS significantly inhibited the phosphorylation of ERKs, TANK\u2010binding kinase 1, and interferon regulatory factor 3 in LPS\u2010PG\u2010stimulated PDLFs, in addition to inhibiting the degradation of I\u03baB. Furthermore, LIPUS treatment reduced messenger RNA (mRNA) expression of\u00a0interleukin\u20101alpha (<jats:italic>IL\u20101alpha<\/jats:italic>), <jats:italic>IL\u20101beta, IL\u20106, IL\u20108,<\/jats:italic> C\u2010C motif chemokine ligand 2<jats:italic>,<\/jats:italic> C\u2010X\u2010C motif chemokine ligand 1 (<jats:italic>CXCL1<\/jats:italic>), <jats:italic>CXCL10<\/jats:italic> and receptor activator of nuclear factor kappa\u2010B ligand, and also diminished IL\u20101\u00df and\u00a0tumor necrosis factor a (TNFa)\u2010induced inflammatory reactions. Phosphorylation of Rho\u2010associated kinase 1 (ROCK1) was induced by LIPUS, while ROCK1\u2010specific inhibitor prevented the promotive effects of LIPUS on p38 phosphorylation, mRNA expression of <jats:italic>CXCL1<\/jats:italic> and <jats:italic>Noggin<\/jats:italic>, and osteogenesis. The suppressive effects of LIPUS on LPS\u2010PG\u2010stimulated inflammatory reactions were also prevented by ROCK1 inhibition. Moreover, LIPUS treatment blocked inhibitory effects of LPS\u2010PG and IL\u20101\u00df on osteogenesis. These results indicate that LIPUS suppresses inflammatory effects of LPS\u2010PG, IL\u20101\u00df, and TNFa and also promotes BMP9\u2010induced osteogenesis through ROCK1 in PDLFs.<\/jats:p>","DOI":"10.1002\/jcb.28727","type":"journal-article","created":{"date-parts":[[2019,4,22]],"date-time":"2019-04-22T06:36:39Z","timestamp":1555914999000},"page":"14657-14669","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["Low\u2010intensity pulsed ultrasound promotes bone morphogenic protein 9\u2010induced osteogenesis and suppresses inhibitory effects of inflammatory cytokines on cellular responses via Rho\u2010associated kinase 1 in human periodontal ligament fibroblasts"],"prefix":"10.1002","volume":"120","author":[{"given":"Joji","family":"Kusuyama","sequence":"first","affiliation":[{"name":"Department of Oral Biochemistry, Field of Developmental Medicine Kagoshima University Graduate School of Medical and Dental Sciences 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