T cell protein tyrosine phosphatase deficiency results in spontaneous synovitis and subchondral bone resorption in mice
KM Doody, S Bussières‐Marmen, A Li… - Arthritis & …, 2012 - Wiley Online Library
Arthritis & Rheumatism, 2012•Wiley Online Library
Objective T cell protein tyrosine phosphatase (TC‐PTP) is an important regulator of
hematopoiesis and cytokine signaling. Recently, several genome‐wide association studies
have identified single‐nucleotide polymorphisms (SNPs) in the locus of TC‐PTP that are
associated with rheumatoid arthritis and juvenile idiopathic arthritis, among other
autoimmune diseases. The aim of this study was to evaluate the effect of TC‐PTP deficiency
on the bone and joint environment using a knockout mouse model. Methods Radiographic …
hematopoiesis and cytokine signaling. Recently, several genome‐wide association studies
have identified single‐nucleotide polymorphisms (SNPs) in the locus of TC‐PTP that are
associated with rheumatoid arthritis and juvenile idiopathic arthritis, among other
autoimmune diseases. The aim of this study was to evaluate the effect of TC‐PTP deficiency
on the bone and joint environment using a knockout mouse model. Methods Radiographic …
Objective
T cell protein tyrosine phosphatase (TC‐PTP) is an important regulator of hematopoiesis and cytokine signaling. Recently, several genome‐wide association studies have identified single‐nucleotide polymorphisms (SNPs) in the locus of TC‐PTP that are associated with rheumatoid arthritis and juvenile idiopathic arthritis, among other autoimmune diseases. The aim of this study was to evaluate the effect of TC‐PTP deficiency on the bone and joint environment using a knockout mouse model.
Methods
Radiographic and micro–computed tomography analyses were performed on femurs of 3‐week‐old mice. In addition, the femorotibial joints were assessed by histology, flow cytometry, and cytokine detection.
Results
Deficiency of TC‐PTP resulted in decreased bone volume as well as an increase in osteoclast density within the mouse femurs. In addition, synovitis, characterized by infiltration of mixed inflammatory cell types and proinflammatory cytokines, developed in the knee joints of TC‐PTP−/− mice.
Conclusion
These findings demonstrate that loss of TC‐PTP expression results in synovitis with several hallmarks of inflammatory arthritis. The inflammatory environment observed in the knee joints of TC‐PTP−/− mice differs from the systemic inflammation previously described in these mice and merits further research into the role of TC‐PTP in the synovium. Furthermore, the results support recently described associations between SNPs in the TC‐PTP locus and arthritis incidence.
Wiley Online Library