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http://purl.uniprot.org/citations/21702022http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/21702022http://www.w3.org/2000/01/rdf-schema#comment"

Objective

Parathyroid hormone-related 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.

Methods

Control sequences of growth differentiation factor 5 were used to delete PTHrP from articular chondrocytes in the mid-region 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-course 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).

Results

The time-course study revealed degenerative changes in only a minority of the KO mice. In the DMM model, male KO mice were highly susceptible to DMM-induced degenerative changes (mean ± SEM total histologic score 45 ± 2.7 in KO mice versus 23 ± 1.4 in controls; P < 0.0001 by Mann-Whitney 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-PTHrP axis is capable of compensating in response to a partial Cre-driven 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.

Conclusion

PTHrP may regulate articular chondrocyte maintenance in mice."xsd:string
http://purl.uniprot.org/citations/21702022http://purl.org/dc/terms/identifier"doi:10.1002/art.30515"xsd:string
http://purl.uniprot.org/citations/21702022http://purl.uniprot.org/core/author"Liang G."xsd:string
http://purl.uniprot.org/citations/21702022http://purl.uniprot.org/core/author"Broadus A.E."xsd:string
http://purl.uniprot.org/citations/21702022http://purl.uniprot.org/core/author"Nasiri A."xsd:string
http://purl.uniprot.org/citations/21702022http://purl.uniprot.org/core/author"Macica C."xsd:string
http://purl.uniprot.org/citations/21702022http://purl.uniprot.org/core/date"2011"xsd:gYear
http://purl.uniprot.org/citations/21702022http://purl.uniprot.org/core/name"Arthritis Rheum"xsd:string
http://purl.uniprot.org/citations/21702022http://purl.uniprot.org/core/pages"3333-3343"xsd:string
http://purl.uniprot.org/citations/21702022http://purl.uniprot.org/core/title"Genetic evidence of the regulatory role of parathyroid hormone-related protein in articular chondrocyte maintenance in an experimental mouse model."xsd:string
http://purl.uniprot.org/citations/21702022http://purl.uniprot.org/core/volume"63"xsd:string
http://purl.uniprot.org/citations/21702022http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/21702022
http://purl.uniprot.org/citations/21702022http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/21702022
http://purl.uniprot.org/uniprot/#_Q540C1-mappedCitation-21702022http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/21702022
http://purl.uniprot.org/uniprot/#_P22858-mappedCitation-21702022http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/21702022
http://purl.uniprot.org/uniprot/#_Q811S6-mappedCitation-21702022http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/21702022
http://purl.uniprot.org/uniprot/#_Q924X4-mappedCitation-21702022http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/21702022
http://purl.uniprot.org/uniprot/Q811S6http://purl.uniprot.org/core/mappedCitationhttp://purl.uniprot.org/citations/21702022
http://purl.uniprot.org/uniprot/Q924X4http://purl.uniprot.org/core/mappedCitationhttp://purl.uniprot.org/citations/21702022
http://purl.uniprot.org/uniprot/P22858http://purl.uniprot.org/core/mappedCitationhttp://purl.uniprot.org/citations/21702022
http://purl.uniprot.org/uniprot/Q540C1http://purl.uniprot.org/core/mappedCitationhttp://purl.uniprot.org/citations/21702022