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

Abstract

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 humans. In this rat model, occlusion of the epiphyseal vessels occurs as a result of a breakdown of the mechanically vulnerable epiphysis. The postnatal development of the epiphysis recapitulates the serial events of the endochondral ossification (i.e., cartilage formation), chondrocyte hypertrophy, cartilage mineralization, vascularization, and introduction of osteoblasts that form the secondary ossification center within the epiphysis. In the present study, a detailed radiographic and histological analysis demonstrates that the osteonecrosis is preceded by a disturbance of the cartilage mineralization and a disturbance of the ossification, despite a normal hypertrophy of the epiphyseal cartilage. These observations suggest that abnormal development of the femoral epiphysis occurs much earlier than manifestation of the osteonecrosis. They lead us to a hypothesis that yet-unclarified transitional events between the cartilage hypertrophy and the cartilage mineralization may be affected in SHRs. Type X collagen is a developmentally regulated matrix molecule that is implicated in the mineralization of the hypertrophied chondrocytes. We show that the expression of type X collagen during epiphyseal ossification is delayed in SHRs (

Roles of Growth Hormone and Insulin-like Growth Factor 1 in Mouse Postnatal Growth

“…In rodents, immunoreactivity for IGF1, and also for type 1 IGF receptor (IGF1R), was detected in cells of the articular and epiphyseal cartilage, secondary ossification centers, proliferating (but not hypertrophic) chondrocytes, and bone marrow cells (Joseph et al, 1999;Maor and Karnieli, 1999;Kikkawa et al, 2000). On the other hand, Igf1 expression examined in rats and mice by in situ hybridization at various postnatal ages up to 7 weeks (Shinar et al, 1993;Wang et al, 1995) indicated the presence of transcripts in perichondrium, periosteum, and presumptive osteoblasts of epiphyseal and metaphyseal trabecular bone, but not in growth plate chondrocytes, which nevertheless appeared to express Igf1r (Wang et al, 1995).…”

Animal Models of Osteonecrosis

“…There is a disturbed ossification in the proximal femoral epiphysis and systemic skeletal growth retardation [30,31]. Kikkawa et al [32] observed that osteonecrosis was actually preceded by a disturbance of cartilage mineralization and abnormal development of the femoral epiphysis. Little et al [33] used this model to evaluate the use of zoledronic acid, a bisphosphonate, as a treatment for Perthes.…”

ACTH protects against glucocorticoid-induced osteonecrosis of bone

“…However, there is strong evidence for an ischemic component. For example, studies using a rat model of Legg-Calve-Perthe's disease suggest that the intracortical blockade of lateral epiphyseal arteries that supply approximately 80% of the femoral head (7) can, in part, be attributed to their anatomical predisposition. It is nonetheless unclear whether ischemia is the initiating event or is secondary to local cellular or vascular bed damage (8).…”