Altered postnatal expression of insulin-like growth factor-I (IGF-I) and type X collagen preceding the Perthes' disease-like lesion of a rat model

The spontaneously hypertensive rat (SHR) is a widely used animal model for the study of hypertension. It also exhibits an osteonecrosis of the femoral epiphysis that resembles the clinical features of Perthes' disease in huma ns. In this rat model, occlusion of the epiphyseal vessels occurs as a resu lt of a breakdown of the mechanically vulnerable epiphysis. The postnatal d evelopment of the epiphysis recapitulates the serial events of the endochon dral ossification (i.e., cartilage formation), chondrocyte hypertrophy, car tilage mineralization, vascularization, and introduction of osteoblasts tha t form the secondary ossification center within the epiphysis. In the prese nt study, a detailed radiographic and histological analysis demonstrates th at the osteonecrosis is preceded by a disturbance of the cartilage minerali zation and a disturbance of the ossification, despite a normal hypertrophy of the epiphyseal cartilage. These observations suggest that abnormal devel opment of the femoral epiphysis occurs much earlier than manifestation of t he osteonecrosis. They lead us to a hypothesis that yet-unclarified transit ional events between the cartilage hypertrophy and the cartilage mineraliza tion may be affected in SHRs. Type X collagen is a developmentally regulate d matrix molecule that is implicated in the mineralization of the hypertrop hied chondrocytes. We show that the expression of type X collagen during ep iphyseal ossification is delayed in SHRs (vs. normal controls), suggesting disturbed growth and/or differentiation of the epiphyseal chondrocytes. Pos tnatal growth and differentiation of the chondrocytes at least partly depen d on insulin-like growth factor-I (IGF-I), which is produced by the chondro cytes in response to the pituitary growth hormone and stimulates cartilage growth in situ. The present study demonstrates an altered IGF-I expression during early postnatal life in SHRs and suggests that the altered IGF-I exp ression as well as the following delay in upregulation of type X collagen m ay cause the mechanical vulnerability of the femoral epiphysis in SHRs.