{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T21:44:25Z","timestamp":1773092665991,"version":"3.50.1"},"reference-count":46,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2024,1,4]],"date-time":"2024-01-04T00:00:00Z","timestamp":1704326400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal Orthopaedic Research"],"published-print":{"date-parts":[[2024,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Osteoporosis is a chronic disease characterized by reduced bone mass and increased fracture risk, estimated to affect over 10 million people in the United States alone. Drugs used to treat bone loss often come with significant limitations and\/or long\u2010term safety concerns. Proteoglycan\u20104 (PRG4, also known as lubricin) is a mucin\u2010like glycoprotein best known for its boundary lubricating function of articular cartilage. In more recent years, it has been shown that PRG4 has anti\u2010inflammatory properties, contributes to the maintenance of subchondral bone integrity, and patients with <jats:italic>PRG4<\/jats:italic> mutations are osteopenic. However, it remains unknown how PRG4 impacts mechanical and material properties of bone. Therefore, our objective was to perform a phenotyping study of bone in a <jats:italic>Prg4<\/jats:italic> gene trap (GT) mouse (PRG4 deficient). We found that femurs of <jats:italic>Prg4<\/jats:italic> GT mice have altered mechanical, structural, and material properties relative to wildtype littermates. Additionally, <jats:italic>Prg4<\/jats:italic> GT mice have a greater number of calvarial osteoclasts than wildtype mice, but do not have a notable inflammatory serum profile. Finally, <jats:italic>Prg4<\/jats:italic> GT mice do not have an altered rate of bone formation, and exogenous recombinant human PRG4 (rhPRG4) administration inhibited osteoclastogenesis in vitro, suggesting that the skeletal phenotype may be due to changes in bone resorption. Overall, this work demonstrates that PRG4 deficiency affects several integral properties of bone structure, mechanics, and skeletal cell activity, and provides the foundation and insight toward future work evaluating PRG4 as a potential therapeutic target in treating bone loss.<\/jats:p>","DOI":"10.1002\/jor.25772","type":"journal-article","created":{"date-parts":[[2023,12,19]],"date-time":"2023-12-19T08:08:49Z","timestamp":1702973329000},"page":"1231-1243","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["PRG4 deficiency in mice alters skeletal structure, mechanics, and calvarial osteoclastogenesis, and rhPRG4 inhibits in vitro osteoclastogenesis"],"prefix":"10.1002","volume":"42","author":[{"given":"Adam P.","family":"Tanguay","sequence":"first","affiliation":[{"name":"Department of Biomedical Engineering UConn Health Farmington Connecticut USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nikhil G.","family":"Menon","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering UConn Health Farmington Connecticut USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Margaret H.","family":"Boudreau","sequence":"additional","affiliation":[{"name":"Department of Medicine UConn Health Farmington Connecticut USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sandra","family":"Jastrzebski","sequence":"additional","affiliation":[{"name":"Department of Medicine UConn Health Farmington Connecticut USA"},{"name":"Department of Orthopaedic Surgery UConn Health Farmington Connecticut USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paige S.","family":"Woods","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering UConn Health Farmington Connecticut USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Erica A.","family":"Doyle","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering UConn Health Farmington Connecticut USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"W. Brent","family":"Edwards","sequence":"additional","affiliation":[{"name":"Human Performance Laboratory Faculty of Kinesiology, University of Calgary Calgary Alberta Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gregory D.","family":"Jay","sequence":"additional","affiliation":[{"name":"Department of Medicine Brown University Warren Alpert Medical School Providence Rhode Island USA"},{"name":"Department of Engineering Brown University Warren Alpert Medical School Providence Rhode Island USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alix C.","family":"Deymier","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering UConn Health Farmington Connecticut USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joseph","family":"Lorenzo","sequence":"additional","affiliation":[{"name":"Department of Medicine UConn Health Farmington Connecticut USA"},{"name":"Department of Orthopaedic Surgery UConn Health Farmington Connecticut USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sun\u2010Kyeong","family":"Lee","sequence":"additional","affiliation":[{"name":"Center on Aging, UConn Health Farmington Connecticut USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7140-254X","authenticated-orcid":false,"given":"Tannin A.","family":"Schmidt","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering UConn Health Farmington Connecticut USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2024,1,4]]},"reference":[{"key":"e_1_2_8_2_1","first-page":"92","article-title":"Osteoporosis: a review of treatment options","volume":"43","author":"Tu KN","year":"2018","journal-title":"P & T"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1080\/21556660.2019.1677674"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.2147\/TCRM.S138000"},{"key":"e_1_2_8_5_1","unstructured":"Mayo\u2010Clinic Staff.\u00a0(2023) Osteoporosis.https:\/\/www.mayoclinic.org\/diseases-conditions\/osteoporosis\/symptoms-causes\/syc-20351968"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.3390\/jcm10010152"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.3390\/jcm10051140"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI200522263"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaophthalmol.2013.2385"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13075-015-0877-x"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13075-021-02621-9"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep18910"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.exer.2021.108628"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/15496"},{"key":"e_1_2_8_15_1","unstructured":"Boston\u2010Children's\u2010Hospital Camptodactyly Arthropathy Coxa Vara Pericarditis Boston Children's Hospital Center for the Study of Genetic Skeletal Disorders."},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12969-016-0093-5"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.3389\/fped.2022.981938"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.4061\/2011\/569417"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.2214\/ajr.185.2.01850522"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1177\/1759720X12467868"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.3892\/mmr.2022.12615"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41584-022-00749-9"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1677\/JOE-08-0568"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrd3669"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1002\/jor.22207"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.508"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajpath.2011.07.032"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1002\/jor.24378"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.39276"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.exer.2014.06.015"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.141"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1801032"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.1805"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-021-90271-x"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1115\/1.4029176"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-bioeng-062117-121139"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11999-011-1784-3"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2014.09.003"},{"key":"e_1_2_8_39_1","doi-asserted-by":"crossref","unstructured":"Keller T(1994) Predicting the Compressive Mechanical Behavior of Bone Journal of Biomechanics","DOI":"10.1016\/0021-9290(94)90056-6"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a031211"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1111\/eos.12119"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1002\/bies.201800166"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1152\/physiolgenomics.00004.2010"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.matbio.2014.08.008"},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0219697"},{"key":"e_1_2_8_46_1","doi-asserted-by":"publisher","DOI":"10.1177\/0363546516686965"},{"key":"e_1_2_8_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtos.2016.08.004"}],"container-title":["Journal of Orthopaedic Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jor.25772","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,4,27]],"date-time":"2024-04-27T09:18:33Z","timestamp":1714209513000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jor.25772"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,1,4]]},"references-count":46,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2024,6]]}},"alternative-id":["10.1002\/jor.25772"],"URL":"https:\/\/doi.org\/10.1002\/jor.25772","archive":["Portico"],"relation":{},"ISSN":["0736-0266","1554-527X"],"issn-type":[{"value":"0736-0266","type":"print"},{"value":"1554-527X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,1,4]]},"assertion":[{"value":"2023-07-26","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-12-12","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-01-04","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}