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However, previous studies have demonstrated that Midazolam is associated with increased risks of congenital malformations, such as dwarfism, when used during early pregnancy. Recent studies have also demonstrated that Midazolam suppresses osteogenesis of mesenchymal stem cells (\n                    <jats:styled-content style=\"fixed-case\">MSC<\/jats:styled-content>\n                    s). Given that hypertrophic chondrocytes can differentiate into osteoblast and osteocytes and contribute to endochondral bone formation, the effect of Midazolam on chondrogenesis remains unclear. In this study, we applied a human\n                    <jats:styled-content style=\"fixed-case\">MSC<\/jats:styled-content>\n                    line, the\n                    <jats:styled-content style=\"fixed-case\">KP<\/jats:styled-content>\n                    cell, to serve as an in\u00a0vitro model to study the effect of Midazolam on chondrogenesis. We first successfully established an in\u00a0vitro chondrogenic model in a micromass culture or a 2D high\u2010density culture performed with\n                    <jats:styled-content style=\"fixed-case\">TGF<\/jats:styled-content>\n                    \u2010\u03b2\u2010driven chondrogenic induction medium. Treatment of the Midazolam dose\u2010dependently inhibited chondrogenesis, examined using Alcian blue\u2010stained glycosaminoglycans and the expression of chondrogenic markers, such as\n                    <jats:styled-content style=\"fixed-case\">SOX<\/jats:styled-content>\n                    9 and type\n                    <jats:styled-content style=\"fixed-case\">II<\/jats:styled-content>\n                    collagen. Inhibition of Midazolam by peripheral benzodiazepine receptor (\n                    <jats:styled-content style=\"fixed-case\">PBR<\/jats:styled-content>\n                    ) antagonist\n                    <jats:styled-content style=\"fixed-case\">PK<\/jats:styled-content>\n                    11195 or small interfering\n                    <jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content>\n                    rescued the inhibitory effects of Midazolam on chondrogenesis. In addition, Midazolam suppressed transforming growth factor\u2010\u03b2\u2010induced Smad3 phosphorylation, and this inhibitory effect could be rescued using\n                    <jats:styled-content style=\"fixed-case\">PBR<\/jats:styled-content>\n                    antagonist\n                    <jats:styled-content style=\"fixed-case\">PK<\/jats:styled-content>\n                    11195. This study provides a possible explanation for Midazolam\u2010induced congenital malformations of the musculoskeletal system through\n                    <jats:styled-content style=\"fixed-case\">PBR<\/jats:styled-content>\n                    .\n                  <\/jats:p>","DOI":"10.1111\/jcmm.13584","type":"journal-article","created":{"date-parts":[[2018,3,7]],"date-time":"2018-03-07T22:28:44Z","timestamp":1520461724000},"page":"2896-2907","source":"Crossref","is-referenced-by-count":8,"title":["Midazolam inhibits chondrogenesis via peripheral benzodiazepine receptor in human mesenchymal stem cells"],"prefix":"10.1111","volume":"22","author":[{"given":"Yung\u2010Ching","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Cell Biology and Anatomy College of Medicine National Cheng Kung University Tainan Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"King\u2010Chuen","family":"Wu","sequence":"additional","affiliation":[{"name":"Department 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