{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T06:26:01Z","timestamp":1790749561313,"version":"4.1.0"},"reference-count":62,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2023,6,1]],"date-time":"2023-06-01T00:00:00Z","timestamp":1685577600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2023,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Tendons are tension\u2010bearing tissues transmitting force from muscle to bone for body movement. This mechanical loading is essential for tendon development, homeostasis, and healing after injury. While Ca\n                    <jats:sup>2+<\/jats:sup>\n                    signaling has been studied extensively for its roles in mechanotransduction, regulating muscle, bone, and cartilage development and homeostasis, knowledge about Ca\n                    <jats:sup>2+<\/jats:sup>\n                    signaling and the source of Ca\n                    <jats:sup>2+<\/jats:sup>\n                    signals in tendon fibroblast biology are largely unknown. Here, we investigated the function of Ca\n                    <jats:sup>2+<\/jats:sup>\n                    signaling through Ca\n                    <jats:sub>V<\/jats:sub>\n                    1.2 voltage\u2010gated Ca\n                    <jats:sup>2+<\/jats:sup>\n                    channel in tendon formation. Using a reporter mouse, we found that Ca\n                    <jats:sub>V<\/jats:sub>\n                    1.2 is highly expressed in tendon during development and downregulated in adult homeostasis. To assess its function, we generated\n                    <jats:italic>ScxCre;Ca<\/jats:italic>\n                    <jats:sub>\n                      <jats:italic>V<\/jats:italic>\n                    <\/jats:sub>\n                    <jats:italic>1.2<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>TS<\/jats:italic>\n                    <\/jats:sup>\n                    mice that express a gain\u2010of\u2010function mutant Ca\n                    <jats:sub>V<\/jats:sub>\n                    1.2 in tendon. We found that mutant tendons were hypertrophic, with more tendon fibroblasts but decreased cell density. TEM analyses demonstrated increased collagen fibrillogenesis in the hypertrophic tendons. Biomechanical testing revealed that the hypertrophic tendons display higher peak load and stiffness, with no changes in peak stress and elastic modulus. Proteomic analysis showed no significant difference in the abundance of type I and III collagens, but mutant tendons had about two\u2010fold increase in other ECM proteins such as tenascin C, tenomodulin, periostin, type XIV and type VIII collagens, around 11\u2010fold increase in the growth factor myostatin, and significant elevation of matrix remodeling proteins including Mmp14, Mmp2, and cathepsin K. Taken together, these data highlight roles for increased Ca\n                    <jats:sup>2+<\/jats:sup>\n                    signaling through Ca\n                    <jats:sub>V<\/jats:sub>\n                    1.2 on regulating expression of myostatin growth factor and ECM proteins for tendon collagen fibrillogenesis during tendon formation.\n                  <\/jats:p>","DOI":"10.1096\/fj.202300607r","type":"journal-article","created":{"date-parts":[[2023,6,1]],"date-time":"2023-06-01T11:15:24Z","timestamp":1685618124000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Increased Ca\n                    <sup>2+<\/sup>\n                    signaling through Ca\n                    <sub>V<\/sub>\n                    1.2 induces tendon hypertrophy with increased collagen fibrillogenesis and biomechanical properties"],"prefix":"10.1096","volume":"37","author":[{"given":"Haiyin","family":"Li","sequence":"first","affiliation":[{"name":"Center for Musculoskeletal Research University of Rochester Medical Center  Rochester New York USA"},{"name":"Department of Orthopeadics University of Rochester Medical Center  Rochester New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonion","family":"Korcari","sequence":"additional","affiliation":[{"name":"Center for Musculoskeletal Research University of Rochester Medical Center  Rochester New York USA"},{"name":"Department of Biomedical Engineering University of Rochester Medical Center  Rochester New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Ciufo","sequence":"additional","affiliation":[{"name":"Center for Musculoskeletal Research University of Rochester Medical Center  Rochester New York USA"},{"name":"Department of Orthopeadics University of Rochester Medical Center  Rochester New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2384-0171","authenticated-orcid":false,"given":"Christopher L.","family":"Mendias","sequence":"additional","affiliation":[{"name":"Arizona Bone, Joint and Sports Medicine Center  Phoenix Arizona USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott A.","family":"Rodeo","sequence":"additional","affiliation":[{"name":"Sports Medicine and Shoulder Service, Hospital for Special Surgery  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark R.","family":"Buckley","sequence":"additional","affiliation":[{"name":"Center for Musculoskeletal Research University of Rochester Medical Center  Rochester New York USA"},{"name":"Department of Biomedical Engineering University of Rochester Medical Center  Rochester New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7548-6653","authenticated-orcid":false,"given":"Alayna E.","family":"Loiselle","sequence":"additional","affiliation":[{"name":"Center for Musculoskeletal Research University of Rochester Medical Center  Rochester New York USA"},{"name":"Department of Orthopeadics University of Rochester Medical Center  Rochester New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2246-0289","authenticated-orcid":false,"given":"Geoffrey S.","family":"Pitt","sequence":"additional","affiliation":[{"name":"Cardiovascular Research Institute, Weill Cornell Medicine  New York New\u00a0York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5912-5770","authenticated-orcid":false,"given":"Chike","family":"Cao","sequence":"additional","affiliation":[{"name":"Center for Musculoskeletal Research University of 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