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The expression of this channel has been associated with the process of chondrogenesis in adult stem cells as well as several cell lines. Here, we used a chondrogenic reporter (Col2a1-GFP) in murine induced pluripotent stem cells (iPSCs) to examine the hypothesis that TRPV4 serves as both a marker and a regulator of chondrogenesis. Over 21\u2009days of chondrogenesis, iPSCs showed significant increases in Trpv4 expression along with the standard chondrogenic gene markers Sox9, Acan, and Col2a1, particularly in the green fluorescent protein positive (GFP+) chondroprogenitor subpopulation. Increased gene expression for Trpv4 was also reflected by the presence of TRPV4 protein and functional Ca2+ signaling. Daily activation of TRPV4 using the specific agonist GSK1016790A resulted in significant increases in cartilaginous matrix production. An improved understanding of the role of TRPV4 in chondrogenesis may provide new insights into the development of new therapeutic approaches for diseases of cartilage, such as osteoarthritis, or channelopathies and hereditary disorders that affect cartilage during development. Harnessing the role of TRPV4 in chondrogenesis may also provide a novel approach for accelerating stem cell differentiation in functional tissue engineering of cartilage replacements for joint repair.<\/jats:p>","DOI":"10.1002\/stem.3440","type":"journal-article","created":{"date-parts":[[2021,11,11]],"date-time":"2021-11-11T04:59:27Z","timestamp":1636606767000},"page":"1447-1456","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":35,"title":["Transient Receptor Potential Vanilloid 4 as a Regulator of Induced Pluripotent Stem Cell Chondrogenesis"],"prefix":"10.1093","volume":"39","author":[{"given":"Vincent P.","family":"Willard","sequence":"first","affiliation":[{"name":"Cytex Therapeutics, Inc, Durham, North Carolina, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1604-2876","authenticated-orcid":false,"given":"Holly A.","family":"Leddy","sequence":"additional","affiliation":[{"name":"Shared Materials Instrumentation Facility \u00a0Duke University, Durham, North Carolina, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Palmer","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery \u00a0Washington University, St. Louis, Missouri, USA"},{"name":"Center of Regenerative Medicine \u00a0Washington University, St. Louis, Missouri, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chia-Lung","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery \u00a0Washington University, St. Louis, Missouri, USA"},{"name":"Department of Orthopaedic Surgery and Rehabilitation, Center for Musculoskeletal Research \u00a0University of Rochester, Rochester, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wolfgang","family":"Liedtke","sequence":"additional","affiliation":[{"name":"Regeneron Pharmaceuticals, Tarrytown, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7380-0330","authenticated-orcid":false,"given":"Farshid","family":"Guilak","sequence":"additional","affiliation":[{"name":"Cytex Therapeutics, Inc, Durham, North Carolina, USA"},{"name":"Center of Regenerative Medicine \u00a0Washington University, St. Louis, Missouri, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2021,8,24]]},"reference":[{"key":"2022022511281011900_stem3440-bib-0001","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1016\/S0092-8674(00)00143-4","article-title":"Vanilloid receptor-related osmotically activated channel (VR-OAC), a candidate vertebrate 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