{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T15:12:13Z","timestamp":1772118733156,"version":"3.50.1"},"reference-count":51,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2023,7,11]],"date-time":"2023-07-11T00:00:00Z","timestamp":1689033600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100013220","name":"Ultragenyx Pharmaceutical","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100013220","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["asbmr.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["JBMR Plus"],"published-print":{"date-parts":[[2023,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Degenerative osteoarthritis (OA) is recognized as an early\u2010onset comorbidity of X\u2010linked hypophosphatemia (XLH), contributing to pain and stiffness and limiting range of motion and activities of daily living. Here, we extend prior findings describing biochemical and cellular changes of articular cartilage (AC) in the phosphate\u2010wasting environment of XLH to determine the impact of these changes on the biomechanical properties of AC in compression and potential role in the etiology of OA. We hypothesize that despite increased proteoglycan biosynthesis, disruption of the mineralized zone of AC impacts the mechanical properties of cartilage that function to accommodate loads and that therapeutic restoration of this zone will improve the mechanical properties of AC. Data were compared between three groups: wild type (WT), Hyp, and Hyp mice treated with calcitriol and oral phosphate. EPIC microCT confirmed AC mineral deficits and responsiveness to therapy. MicroCT of the Hyp subchondral bone plate revealed that treatment improved trabecular bone volume (BV\/TV) but remained significantly lower than WT mice in other trabecular microstructures (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.05). Microindentation AC studies revealed that, compared with WT mice, the mean stiffness of tibial AC was significantly lower in untreated Hyp mice (2.65\u2009\u00b1\u20090.95 versus 0.87\u2009\u00b1\u20090.33\u2009N\/mm,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.001) and improved with therapy (2.15\u2009+\u20090.38\u2009N\/mm) to within WT values. Stress relaxation of AC under compressive loading displayed similar biphasic relaxation time constants (Tau\n                    <jats:sub>fast<\/jats:sub>\n                    and Tau\n                    <jats:sub>slow<\/jats:sub>\n                    ) between controls and Hyp mice, although Tau\n                    <jats:sub>slow<\/jats:sub>\n                    trended toward slowed relaxation times. In addition, Tau\n                    <jats:sub>fast<\/jats:sub>\n                    and Tau\n                    <jats:sub>slow<\/jats:sub>\n                    times correlated with peak load in WT mice (\n                    <jats:italic>r<\/jats:italic>\n                    \u2009=\u20090.80;\n                    <jats:italic>r<\/jats:italic>\n                    \u2009=\u20090.78, respectively), whereas correlation coefficient values for Hyp mice (\n                    <jats:italic>r<\/jats:italic>\n                    \u2009=\u20090.46;\n                    <jats:italic>r<\/jats:italic>\n                    \u2009=\u20090.21) improved with treatment (\n                    <jats:italic>r<\/jats:italic>\n                    \u2009=\u20090.71;\n                    <jats:italic>r<\/jats:italic>\n                    \u2009=\u20090.56). These data provide rationale for therapies that both preserve AC stiffness and recovery from compression. The Hyp mouse also provides unique insight into determinants of structural stiffness and the viscoelastic properties of AC in the progression of OA. \u00a9 2023 The Authors.\n                    <jats:italic>JBMR Plus<\/jats:italic>\n                    published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.\n                  <\/jats:p>","DOI":"10.1002\/jbm4.10796","type":"journal-article","created":{"date-parts":[[2023,7,12]],"date-time":"2023-07-12T01:30:33Z","timestamp":1689125433000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Biomechanical Impact of Phosphate Wasting on Articular Cartilage Using the Murine Hyp Model of X\u2010linked hypophosphatemia"],"prefix":"10.1093","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1760-9678","authenticated-orcid":false,"given":"Carolyn M","family":"Macica","sequence":"first","affiliation":[{"name":"Connecticut Children's Research Institute  Hartford CT USA"},{"name":"Department of Pharmacology Yale University School of Medicine  New Haven CT USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5118-5867","authenticated-orcid":false,"given":"Steven M","family":"Tommasini","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics and Rehabilitation Yale University School of Medicine  New Haven CT USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2023,7,11]]},"reference":[{"key":"e_1_2_9_2_1","volume-title":"The Burden of Musculoskeletal Diseases in the United States (BMUS)","author":"United States Bone and Joint Initiative","year":"2014"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10545-018-0147-6"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.17294\/2330-0698.1727"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00223-011-9502-4"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1210\/clinem\/dgaa064"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1530\/EJE-15-0661"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2020.00854"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13023-019-1014-8"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1097\/00005792-198911000-00002"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1148\/radiology.171.2.2539609"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1210\/js.2018-00365"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/bies.950171208"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.joca.2015.05.012"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/jor.1100120506"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/0142-9612(92)90001-5"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1115\/1.1531656"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1023\/B:ABME.0000017541.82498.37"},{"key":"e_1_2_9_19_1","unstructured":"RuppeMD.X\u2010linked hypophosphatemia. 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