{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T16:28:55Z","timestamp":1773073735933,"version":"3.50.1"},"reference-count":48,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2011,10,28]],"date-time":"2011-10-28T00:00:00Z","timestamp":1319760000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Arthritis &amp; Rheumatism"],"published-print":{"date-parts":[[2011,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>Parathyroid hormone\u2013related protein (PTHrP) regulates the rate of differentiation of growth chondrocytes and is also expressed in articular chondrocytes. This study tested the hypothesis that PTHrP might have a regulatory role in articular chondrocyte maintenance.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Control sequences of growth differentiation factor 5 were used to delete PTHrP from articular chondrocytes in the mid\u2010region of mouse articular cartilage. Mice with conditional deletion of PTHrP (knockout [KO]) and littermate control mice were evaluated for degenerative changes using both a time\u2010course design and destabilization of the medial meniscus (DMM) technique. A total histologic score of degenerative changes was determined for the femoral and tibial articular surfaces (total maximum score of 60).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The time\u2010course study revealed degenerative changes in only a minority of the KO mice. In the DMM model, male KO mice were highly susceptible to DMM\u2010induced degenerative changes (mean \u00b1 SEM total histologic score 45 \u00b1 2.7 in KO mice versus 23 \u00b1 1.4 in controls; <jats:italic>P<\/jats:italic> &lt; 0.0001 by Mann\u2010Whitney U test), with virtually no overlap between groups. PTHrP normally functions in a feedback loop with Indian hedgehog (IHH), in which a reduction in one signaling partner induces a compensatory increase in the other. A number of phenotypic and functional markers were documented in KO mice to suggest that the IHH\u2013PTHrP axis is capable of compensating in response to a partial Cre\u2010driven PTHrP deletion, a finding that underscores the need to subject the mouse articular cartilage to a destabilizing challenge in order to elicit frankly degenerative findings.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>PTHrP may regulate articular chondrocyte maintenance in mice.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.30515","type":"journal-article","created":{"date-parts":[[2011,6,23]],"date-time":"2011-06-23T20:00:45Z","timestamp":1308859245000},"page":"3333-3343","source":"Crossref","is-referenced-by-count":31,"title":["Genetic evidence of the regulatory role of parathyroid hormone\u2013related protein in articular chondrocyte maintenance in an experimental mouse 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