AUTHOR=Wehenkel Marie , Corr Maripat , Guy Clifford S. , Edwards Benjamin A. , Castellaw Ashley H. , Calabrese Christopher , Pagès Gilles , Pouysségur Jacques , Vogel Peter , McGargill Maureen A. 

TITLE=Extracellular Signal-Regulated Kinase Signaling in CD4-Expressing Cells Inhibits Osteochondromas

JOURNAL=Frontiers in Immunology

VOLUME=8

YEAR=2017

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2017.00482

DOI=10.3389/fimmu.2017.00482

ISSN=1664-3224

ABSTRACT=<p>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 <italic>Erk1</italic> and a conditional deletion of <italic>Erk2</italic> 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 <italic>Erk2</italic> in the T cells. Rather, <italic>CD4cre</italic> 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.</p>