{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T12:44:03Z","timestamp":1787316243627,"version":"build-2736575974"},"reference-count":57,"publisher":"Oxford University Press (OUP)","issue":"9","license":[{"start":{"date-parts":[[2025,9,19]],"date-time":"2025-09-19T00:00:00Z","timestamp":1758240000000},"content-version":"vor","delay-in-days":18,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000038","name":"Natural Sciences and Engineering Research Council","doi-asserted-by":"crossref","award":["RGPIN-2014-04586"],"award-info":[{"award-number":["RGPIN-2014-04586"]}],"id":[{"id":"10.13039\/501100000038","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100000196","name":"Canada Foundation for Innovation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000196","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100012260","name":"Calgary Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100012260","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Grace Glaum Professorship"},{"DOI":"10.13039\/501100001804","name":"Canada Research Chairs","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001804","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,9,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Proteoglycan 4 (PRG4), also known as lubricin, is essential for maintaining tissue homeostasis and acts as a lubricant that protects joint surfaces from wear and tear. Our previous studies have demonstrated that PRG4 plays multiple roles in wound healing in mice and pigs. Specifically, PRG4 derived from Hic1+ mesenchymal progenitor cells (MPCs) is crucial for maintaining tissue homeostasis in the dura mater near the spinal cord, and in the skin it contributes to ear wound healing in mice. Additionally, mice lacking PRG4 exhibit abnormal bone structure and function. However, the role of PRG4 in fracture healing remains unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>To investigate the role of PRG4 in fracture repair, we generated mice with a conditional deletion of Prg4 in the Hic1+ lineage. The presence and contribution of Hic1+ progenitors at the fracture site were assessed at 2\u2011 and 4\u2011weeks post\u2011injury (wpi). Bone healing quality was evaluated, and the cellular phenotype within the fracture callus was examined.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>We observed Hic1+ progenitors at the fracture site at both 2\u2011 and 4\u2011wpi. Conditional deletion of Prg4 in these progenitors impaired the quality of new bone formation at the fracture site. Furthermore, PRG4 was required to maintain the cartilaginous phenotype of callus cells. In its absence, chondrocytes underwent premature transformation into osteoblasts, disrupting the normal progression of fracture healing.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>These findings provide new insights into the role of PRG4 in bone regeneration. PRG4, derived from Hic1+ MPCs, is critical for regulating the balance between chondrogenesis and osteogenesis during fracture repair. By preventing premature chondrocyte\u2011to\u2011osteoblast transition, PRG4 supports proper callus formation and bone healing. This work highlights the importance of PRG4 and Hic1+ MPCs in fracture repair and extends their known functions in tissue homeostasis and wound healing.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/stcltm\/szaf043","type":"journal-article","created":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T11:52:59Z","timestamp":1753876379000},"source":"Crossref","is-referenced-by-count":3,"title":["Mesenchymal progenitor\u2013derived proteoglycan 4 regulates the transdifferentiation of chondrocytes into osteoblasts during fracture healing"],"prefix":"10.1093","volume":"14","author":[{"given":"Nicoletta","family":"Ninkovic","sequence":"first","affiliation":[{"name":"McCaig Institute for Bone & Joint Health, University of Calgary , Calgary, AB T2N4N1,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica May","family":"Corpuz","sequence":"additional","affiliation":[{"name":"McCaig Institute for Bone & Joint Health, University of Calgary , Calgary, AB T2N4N1,","place":["Canada"]},{"name":"Department of Biomedical Engineering, University of Calgary , Calgary, AB T2N4N1,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alana","family":"Stahl","sequence":"additional","affiliation":[{"name":"McCaig Institute for Bone & Joint Health, University of Calgary , Calgary, AB T2N4N1,","place":["Canada"]},{"name":"Department of Biomedical Engineering, University of Calgary , Calgary, AB T2N4N1,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra","family":"Olsen","sequence":"additional","affiliation":[{"name":"McCaig Institute for Bone & Joint Health, University of Calgary , Calgary, AB T2N4N1,","place":["Canada"]},{"name":"Department of Biomedical Engineering, University of Calgary , Calgary, AB T2N4N1,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Colton M","family":"Unger","sequence":"additional","affiliation":[{"name":"McCaig Institute for Bone & Joint Health, University of Calgary , Calgary, AB T2N4N1,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aria Ahadzadeh","family":"Ardebili","sequence":"additional","affiliation":[{"name":"McCaig Institute for Bone & Joint Health, University of Calgary , Calgary, AB T2N4N1,","place":["Canada"]},{"name":"Department of Biomedical Engineering, University of Calgary , Calgary, AB T2N4N1,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haochen","family":"Sun","sequence":"additional","affiliation":[{"name":"McCaig Institute for Bone & Joint Health, University of Calgary , Calgary, AB T2N4N1,","place":["Canada"]},{"name":"Department of Biomedical Engineering, University of Calgary , Calgary, AB T2N4N1,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juyeon","family":"Cha","sequence":"additional","affiliation":[{"name":"McCaig Institute for Bone & Joint Health, University of Calgary , Calgary, AB T2N4N1,","place":["Canada"]},{"name":"Department of Biomedical Engineering, University of Calgary , Calgary, AB T2N4N1,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daphne","family":"Kaketsis","sequence":"additional","affiliation":[{"name":"McCaig Institute for Bone & Joint Health, University of Calgary , Calgary, AB T2N4N1,","place":["Canada"]},{"name":"Department of Biomedical Engineering, University of Calgary , Calgary, AB T2N4N1,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah L","family":"Manske","sequence":"additional","affiliation":[{"name":"McCaig Institute for Bone & Joint Health, University of Calgary , Calgary, AB T2N4N1,","place":["Canada"]},{"name":"Department of Biomedical Engineering, University of Calgary , Calgary, AB T2N4N1,","place":["Canada"]},{"name":"Department of Radiology, University of Calgary , Calgary, AB T2N4N1,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ifaz T","family":"Haider","sequence":"additional","affiliation":[{"name":"McCaig Institute for Bone & Joint Health, University of Calgary , Calgary, AB T2N4N1,","place":["Canada"]},{"name":"Human Performance Laboratory, Faculty of Kinesiology, University of Calgary , Calgary, AB T2N4N1,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ralph S","family":"Marcucio","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery, University of California at San Francisco , San Francisco, CA 94110,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tannin A","family":"Schmidt","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, University of Connecticut Health Center , Farmington, CT 06030,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregory D","family":"Jay","sequence":"additional","affiliation":[{"name":"Department of Emergency Medicine, Alpert Medical School of Brown University , Providence, RI 02903,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T Michael","family":"Underhill","sequence":"additional","affiliation":[{"name":"Department of Cellular and Physiological Sciences, University of British Columbia , Vancouver, BC V6T1Z3,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"W Brent","family":"Edwards","sequence":"additional","affiliation":[{"name":"McCaig Institute for Bone & Joint Health, University of Calgary , Calgary, AB T2N4N1,","place":["Canada"]},{"name":"Department of Biomedical Engineering, University of Calgary , Calgary, AB T2N4N1,","place":["Canada"]},{"name":"Human Performance Laboratory, Faculty of Kinesiology, University of Calgary , Calgary, AB T2N4N1,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Derrick E","family":"Rancourt","sequence":"additional","affiliation":[{"name":"McCaig Institute for Bone & Joint Health, University of Calgary , Calgary, AB T2N4N1,","place":["Canada"]},{"name":"Department of Biomedical Engineering, University of Calgary , Calgary, AB T2N4N1,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeff","family":"Biernaskie","sequence":"additional","affiliation":[{"name":"Faculty of Veterinary Medicine, University of Calgary , Calgary, AB T2N4N1,","place":["Canada"]},{"name":"Alberta Children\u2019s Hospital Research Institute, University of Calgary , Calgary, AB 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