Erk2 is a critical regulator of spontaneous osteochondromas (P1016)

Abstract Osteochondromatosis is the most frequent tumor of the skeletal system. Although these bone tumors are benign, they create deformities resulting in impaired use of the affected joints, severe pain, and potential paralysis due to nerve compression. Patients often have a single tumor, although a disorder characterized by the presence of multiple osteochondromas is well established. Surprisingly, mice with a germline deficiency in Erk1 bred to mice with a conditional deletion of Erk2 in the T cell lineage (Erk1-/-.Erk2fl/fl.CD4cre) [DKO] developed multiple osteochondromas by 28 weeks of age. Gross protrusions of the spine and carpus were visible in the DKO mice, and radiological imaging revealed boney abnormalities in the spine, carpus, and sternum. Histological analysis of these protrusions showed an excessive proliferation of cartilage originating from the growth plates, but no mononuclear infiltrate indicative of inflammation. Moreover, we did not find autoantibodies in the serum of the DKO mice. Flow cytometric analysis indicated that an innate-like population of cells was more prominent in the DKO mice compared to littermate controls. These data suggest that the presence of Erk2 in a CD4-expressing, non-T cell population may play a central role in preventing the development of osteochondromas.