| Autor: |
Wehenkel M; Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN, USA., Corr M; Division of Rheumatology, Allergy, and Immunology, University of California San Diego, La Jolla, CA, USA., Guy CS; Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN, USA., Edwards BA; Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN, USA., Castellaw AH; Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN, USA., Calabrese C; Department of Veterinary Pathology, St. Jude Children's Research Hospital, Memphis, TN, USA., Pagès G; Institute for Research of Cancer and Aging (IRCAN), University of Nice Sophia-Antipolis, Nice, France., Pouysségur J; Institute for Research of Cancer and Aging (IRCAN), University of Nice Sophia-Antipolis, Nice, France.; Centre Scientifique de Monaco (CSM), Monaco, France., Vogel P; Department of Veterinary Pathology, St. Jude Children's Research Hospital, Memphis, TN, USA., McGargill MA; Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN, USA. |
| Abstrakt: |
Defects in cartilage homeostasis can give rise to various skeletal disorders including osteochondromas. Osteochondromas are benign bone tumors caused by excess accumulation of chondrocytes, the main cell type of cartilage. The extracellular signal-regulated kinase (ERK) pathway is a major signaling node that functions within chondrocytes to regulate their growth and differentiation. However, it is not known whether the ERK pathway in other cell types regulates cartilage homeostasis. We show here that mice with a germline deficiency of Erk1 and a conditional deletion of Erk2 in cells that express CD4, or expressed CD4 at one point in development, unexpectedly developed bone deformities. The bone lesions were due to neoplastic outgrowths of chondrocytes and disordered growth plates, similar to tumors observed in the human disease, osteochondromatosis. Chondrocyte accumulation was not due to deletion of Erk2 in the T cells. Rather, CD4cre was expressed in cell types other than T cells, including a small fraction of chondrocytes. Surprisingly, the removal of T cells accelerated osteochondroma formation and enhanced disease severity. These data show for the first time that T cells impact the growth of osteochondromas and describe a novel model to study cartilage homeostasis and osteochondroma formation. |
