{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,25]],"date-time":"2026-07-25T00:56:52Z","timestamp":1784941012796,"version":"3.55.0"},"reference-count":91,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2025,1,17]],"date-time":"2025-01-17T00:00:00Z","timestamp":1737072000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 HD113224-01"],"award-info":[{"award-number":["R01 HD113224-01"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Ruth L. Kirschstein National Service Research Postdoctoral Fellowship","award":["F32 HD103314-01"],"award-info":[{"award-number":["F32 HD103314-01"]}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,4,13]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Reproductive success requires accurately timed remodeling of the cervix to orchestrate the maintenance of pregnancy, the process of labor, and birth. Prior work in mice established that a combination of continuous turnover of fibrillar collagen and reduced formation of collagen cross-links allows for the gradual increase in tissue compliance and delivery of the fetus during labor. However, the mechanism for continuous collagen degradation to ensure turnover during cervical remodeling is still unknown. This study demonstrates the functional role of extracellular and intracellular collagen degradative pathways in two different settings of cervical remodeling: physiological term remodeling and inflammation-mediated premature remodeling. Extracellular collagen degradation is achieved by the activity of fibroblast-derived matrix metalloproteases MMP14, MMP2, and fibroblast activation protein (FAP). In parallel, we demonstrate the function of an intracellular collagen degradative pathway in fibroblast cells mediated by the collagen endocytic mannose receptor type-2 (MRC2). These pathways appear to be functionally redundant as loss of MRC2 does not obstruct collagen turnover or cervical function in pregnancy. While both extracellular and intracellular pathways are also utilized in inflammation-mediated premature cervical remodeling, the extracellular collagen degradation pathway uniquely employs fibroblast and immune-cell-derived proteases. In sum, these findings identify the dual utilization of two distinct degradative pathways as a failsafe mechanism to achieve continuous collagen turnover in the cervix, thereby allowing dynamic shifts in cervical tissue mechanics and function.<\/jats:p>","DOI":"10.1093\/biolre\/ioaf012","type":"journal-article","created":{"date-parts":[[2025,1,17]],"date-time":"2025-01-17T18:28:47Z","timestamp":1737138527000},"page":"709-727","source":"Crossref","is-referenced-by-count":12,"title":["Collagen turnover during cervical remodeling involves both intracellular and extracellular collagen degradation pathways"],"prefix":"10.1093","volume":"112","author":[{"given":"Mariano","family":"Colon-Caraballo","sequence":"first","affiliation":[{"name":"Department of Ob\/Gyn and Cecil H. and Ida Green Center for Reproductive Biology Sciences, The University of Texas Southwestern Medical Center , Dallas, Texas ,","place":["United States of America"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Serena R","family":"Russell","sequence":"additional","affiliation":[{"name":"Department of Mechanical Engineering, Columbia University , New York, New York City ,","place":["United States of America"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristin M","family":"Myers","sequence":"additional","affiliation":[{"name":"Department of Mechanical Engineering, Columbia University , New York, New York City ,","place":["United States of America"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mala","family":"Mahendroo","sequence":"additional","affiliation":[{"name":"Department of Ob\/Gyn and Cecil H. and Ida Green Center for Reproductive Biology Sciences, The University of Texas Southwestern Medical Center , Dallas, Texas ,","place":["United States of America"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2025,1,17]]},"reference":[{"key":"2025041504320661300_ref1","doi-asserted-by":"crossref","first-page":"e681","DOI":"10.1016\/j.ajog.2009.02.034","article-title":"Who is at risk for prolonged and postterm pregnancy?","volume":"200","author":"Caughey","year":"2009","journal-title":"Am J Obstet Gynecol"},{"key":"2025041504320661300_ref2","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1038\/s41586-020-2612-2","article-title":"Effects of extracellular matrix viscoelasticity on cellular behaviour","volume":"584","author":"Chaudhuri","year":"2020","journal-title":"Nature"},{"key":"2025041504320661300_ref3","doi-asserted-by":"crossref","first-page":"1533","DOI":"10.1016\/j.jbiomech.2015.02.060","article-title":"A continuous fiber distribution material model for human cervical tissue","volume":"48","author":"Myers","year":"2015","journal-title":"J 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