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Our previous study showed that low\u2010intensity pulsed ultrasound (LIPUS) did not promote osteogenesis of a murine MSC line C3H10T1\/2, although LIPUS treatment suppressed adipogenesis. Therefore, we investigated the effect of a combination of an osteoinductive factor such as bone morphogenic protein\u20102 (BMP\u20102) and LIPUS treatment on osteogenesis. This combination significantly upregulated the gene expressions of BMP receptors and RUNX2, which is a key early osteogenic transcription factor. Interestingly, cellular communication network factor 1 (CCN1) was significantly increased at the mRNA and protein levels. Additionally,\n                    <jats:italic>Runx2<\/jats:italic>\n                    expression was increased by a recombinant CCN1 protein and decreased in CRISPR\u2010Cas9\u2010generated\n                    <jats:italic>Ccn1<\/jats:italic>\n                    knockout (KO) cells treated with the combination of LIPUS treatment and BMP\u20102. Moreover,\n                    <jats:italic>Runx2<\/jats:italic>\n                    expression was recovered through the transfection of a\n                    <jats:italic>Ccn1<\/jats:italic>\n                    expression plasmid into\n                    <jats:italic>Ccn1<\/jats:italic>\n                    KO cells. These findings indicate that treatment with the combination of LIPUS treatment and BMP\u20102 promoted CCN1 production, and the CCN1 regulates the\n                    <jats:italic>Runx2<\/jats:italic>\n                    expression in C3H10T1\/2 cells, thus suggesting that CCN1 induced by mechanical stimulation and an osteoinductive factor plays a pivotal role in osteogenesis of MSCs.\n                  <\/jats:p>","DOI":"10.1002\/ccs3.70101","type":"journal-article","created":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T16:41:20Z","timestamp":1787762480000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Critical role of cellular communication network factor 1 in early osteogenesis of mesenchymal stem cells primed by low\u2010intensity pulsed ultrasound and bone morphogenetic protein 2"],"prefix":"10.1002","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-3774-9959","authenticated-orcid":false,"given":"Hsu Myat","family":"Paing","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Molecular Dentistry Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences  Okayama Japan"},{"name":"Department of Oral Rehabilitation and Regenerative Medicine Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences  Okayama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0795-5072","authenticated-orcid":false,"given":"Satoshi","family":"Kubota","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Dentistry Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences  Okayama 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