{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T01:08:19Z","timestamp":1773277699634,"version":"3.50.1"},"reference-count":57,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2023,5,18]],"date-time":"2023-05-18T00:00:00Z","timestamp":1684368000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Foundation Nakao for Worldwide Oral Health","award":["2021\u20132022"],"award-info":[{"award-number":["2021\u20132022"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>A micro-physiological system is generally fabricated using soft materials, such as polydimethylsiloxane silicone (PDMS), and seeks an inflammatory osteolysis model for osteoimmunological research as one of the development needs. Microenvironmental stiffness regulates various cellular functions via mechanotransduction. Controlling culture substrate stiffness may help spatially coordinate the supply of osteoclastogenesis-inducing factors from immortalized cell lines, such as mouse fibrosarcoma L929 cells, within the system. Herein, we aimed to determine the effects of substrate stiffness on the osteoclastogenesis-inducing potential of L929 cells via cellular mechanotransduction. L929 cells showed increased expression of osteoclastogenesis-inducing factors when cultured on type I collagen-coated PDMS substrates with soft stiffness, approximating that of soft tissue sarcomas, regardless of the addition of lipopolysaccharide to augment proinflammatory reactions. Supernatants of L929 cells cultured on soft PDMS substrates promoted osteoclast differentiation of the mouse osteoclast precursor RAW 264.7 by stimulating the expression of osteoclastogenesis-related gene markers and tartrate-resistant acid phosphatase activity. The soft PDMS substrate inhibited the nuclear translocation of YES-associated proteins in L929 cells without reducing cell attachment. However, the hard PDMS substrate hardly affected the cellular response of the L929 cells. Our results showed that PDMS substrate stiffness tuned the osteoclastogenesis-inducing potential of L929 cells via cellular mechanotransduction.<\/jats:p>","DOI":"10.3390\/ijms24108959","type":"journal-article","created":{"date-parts":[[2023,5,18]],"date-time":"2023-05-18T08:09:44Z","timestamp":1684397384000},"page":"8959","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Mechanoregulation of Osteoclastogenesis-Inducing Potentials of Fibrosarcoma Cell Line by Substrate Stiffness"],"prefix":"10.3390","volume":"24","author":[{"given":"Watcharaphol","family":"Tiskratok","sequence":"first","affiliation":[{"name":"Division of Molecular and Regenerative Prosthodontics, Tohoku University Graduate School of Dentistry, 4-1 Seiryo-machi, Sendai 980-8575, Miyagi, Japan"},{"name":"School of Geriatric Oral Health, Institute of Dentistry, Suranaree University of Technology, 111 University Rd. Suranaree, Nakhon Ratchasima 30000, Mueang, Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masahiro","family":"Yamada","sequence":"additional","affiliation":[{"name":"Division of Molecular and Regenerative Prosthodontics, Tohoku University Graduate School of Dentistry, 4-1 Seiryo-machi, Sendai 980-8575, Miyagi, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5470-4404","authenticated-orcid":false,"given":"Jun","family":"Watanabe","sequence":"additional","affiliation":[{"name":"Division of Molecular and Regenerative Prosthodontics, Tohoku University Graduate School of Dentistry, 4-1 Seiryo-machi, Sendai 980-8575, Miyagi, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qu","family":"Pengyu","sequence":"additional","affiliation":[{"name":"Division of Molecular and Regenerative Prosthodontics, Tohoku University Graduate School of Dentistry, 4-1 Seiryo-machi, Sendai 980-8575, Miyagi, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0476-0624","authenticated-orcid":false,"given":"Tsuyoshi","family":"Kimura","sequence":"additional","affiliation":[{"name":"Department of Material-Based Medical Engineering, Institute of Biomaterials and Bioengineering, Tokyo Medical and Dental University, Tokyo 101-0062, Chiyoda-ku, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0200-8132","authenticated-orcid":false,"given":"Hiroshi","family":"Egusa","sequence":"additional","affiliation":[{"name":"Division of Molecular and Regenerative Prosthodontics, Tohoku University Graduate School of Dentistry, 4-1 Seiryo-machi, Sendai 980-8575, Miyagi, Japan"},{"name":"Center for Advanced Stem Cell and Regenerative Research, Tohoku University Graduate School of Dentistry, 4-1 Seiryo-machi, Sendai 980-8575, Miyagi, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,5,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1038\/nrd4539","article-title":"Organs-on-chips at the frontiers of drug discovery","volume":"14","author":"Esch","year":"2015","journal-title":"Nat. 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