{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,31]],"date-time":"2026-01-31T05:44:00Z","timestamp":1769838240605,"version":"3.49.0"},"reference-count":41,"publisher":"The Company of Biologists","issue":"22","license":[{"start":{"date-parts":[[2021,11,15]],"date-time":"2021-11-15T00:00:00Z","timestamp":1636934400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/www.biologists.com\/user-licence-1-1\/"}],"funder":[{"name":"Max-Planck-Gesellschaft"},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"crossref","award":["D10041297"],"award-info":[{"award-number":["D10041297"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"crossref","award":["SFB914"],"award-info":[{"award-number":["SFB914"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100002347","name":"Bundesministerium f\u00fcr Bildung und Forschung","doi-asserted-by":"crossref","award":["01GM1912"],"award-info":[{"award-number":["01GM1912"]}],"id":[{"id":"10.13039\/501100002347","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,11,15]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n               <jats:p>Osteoclasts form special integrin-mediated adhesion structures called sealing zones that enable them to adhere to and resorb bone. Sealing zones consist of densely packed podosomes tightly interconnected by actin fibers. Their formation requires the presence of the hematopoietic integrin regulator kindlin-3 (also known as Fermt3). In this study, we investigated osteoclasts and their adhesion structures in kindlin-3 hypomorphic mice expressing only 5\u201310% of the kindlin-3 level of wild-type mice. Low kindlin-3 expression reduces integrin activity, results in impaired osteoclast adhesion and signaling, and delays cell spreading. Despite these defects, in vitro-generated kindlin-3-hypomorphic osteoclast-like cells arrange their podosomes into adhesion patches and belts, but their podosome and actin organization is abnormal. Remarkably, kindlin-3-hypomorphic osteoclasts form sealing zones when cultured on calcified matrix in vitro and on bone surface in vivo. However, functional assays, immunohistochemical staining and electron micrographs of bone sections showed that they fail to seal the resorption lacunae properly, which is required for secreted proteinases to digest bone matrix. This results in mild osteopetrosis. Our study reveals a new, hitherto understudied function of kindlin-3 as an essential organizer of integrin-mediated adhesion structures, such as sealing zones.<\/jats:p>","DOI":"10.1242\/jcs.259040","type":"journal-article","created":{"date-parts":[[2021,10,27]],"date-time":"2021-10-27T09:50:04Z","timestamp":1635328204000},"source":"Crossref","is-referenced-by-count":6,"title":["Low kindlin-3 levels in osteoclasts of kindlin-3 hypomorphic mice result in osteopetrosis due to leaky sealing zones"],"prefix":"10.1242","volume":"134","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4723-056X","authenticated-orcid":false,"given":"Sarah","family":"Klapproth","sequence":"first","affiliation":[{"name":"Institute of Experimental Hematology, School of Medicine, Technical University Munich 1 , D-81675 Munich ,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karsten","family":"Richter","sequence":"additional","affiliation":[{"name":"Central Unit Electron Microscopy, German Cancer Research Center (DKFZ) 2 , D-69120 Heidelberg ,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Clara","family":"T\u00fcrk","sequence":"additional","affiliation":[{"name":"CECAD Research Center, Institute for Genetics, University of Cologne 3 , D-50931 Cologne ,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Theresa","family":"Bock","sequence":"additional","affiliation":[{"name":"CECAD Research Center, Institute for Genetics, University of Cologne 3 , D-50931 Cologne ,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas","family":"Bromberger","sequence":"additional","affiliation":[{"name":"Institute of Experimental Hematology, School of Medicine, Technical University Munich 1 , D-81675 Munich ,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Julian","family":"Dominik","sequence":"additional","affiliation":[{"name":"Walter Brendel Centre of Experimental Medicine, Ludwig-Maximilians-University Munich 4 , 81377 Munich ,","place":["Germany"]},{"name":"Ludwig-Maximilians-University Munich 5 Department of Otorhinolaryngology , , 81377 Munich ,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kathrin","family":"Huck","sequence":"additional","affiliation":[{"name":"Institute of Immunology, University of Heidelberg 6 , D-69120 Heidelberg ,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kristian","family":"Pfaller","sequence":"additional","affiliation":[{"name":"Institute of Histology and Embryology, Medical University Innsbruck 7 , A-6020 Innsbruck ,","place":["Austria"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael W.","family":"Hess","sequence":"additional","affiliation":[{"name":"Institute of Histology and Embryology, Medical University Innsbruck 7 , A-6020 Innsbruck ,","place":["Austria"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christoph A.","family":"Reichel","sequence":"additional","affiliation":[{"name":"Walter Brendel Centre of Experimental Medicine, Ludwig-Maximilians-University Munich 4 , 81377 Munich ,","place":["Germany"]},{"name":"Ludwig-Maximilians-University Munich 5 Department of Otorhinolaryngology , , 81377 Munich ,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marcus","family":"Kr\u00fcger","sequence":"additional","affiliation":[{"name":"CECAD Research Center, Institute for Genetics, University of Cologne 3 , D-50931 Cologne ,","place":["Germany"]},{"name":"Center for Molecular Medicine (CMMC), University of Cologne 8 , D-50931 Cologne ,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Inaam A.","family":"Nakchbandi","sequence":"additional","affiliation":[{"name":"Institute of Immunology, University of Heidelberg 6 , D-69120 Heidelberg ,","place":["Germany"]},{"name":"Max-Planck Institute of Biochemistry 9 , D-82152 Martinsried ,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8825-5566","authenticated-orcid":false,"given":"Markus","family":"Moser","sequence":"additional","affiliation":[{"name":"Institute of Experimental Hematology, School of Medicine, Technical University Munich 1 , D-81675 Munich ,","place":["Germany"]},{"name":"Max-Planck Institute of Biochemistry 9 , D-82152 Martinsried ,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"237","published-online":{"date-parts":[[2021,11,26]]},"reference":[{"key":"2024120214485987300_JCS259040C1","doi-asserted-by":"publisher","first-page":"706","DOI":"10.1359\/jbmr.091011","article-title":"Circulating fibronectin affects bone matrix, whereas osteoblast fibronectin modulates osteoblast function","volume":"25","author":"Bentmann","year":"2010","journal-title":"J. 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