Increased osteocyte apoptosis during the development of femoral head osteonecrosis in spontaneously hypertensive rats

Department of Orthopaedic Surgery, Okayama University Medical School, Japan.
Acta medica Okayama (Impact Factor: 0.7). 04/2000; 54(2):67-74.
Source: PubMed


We investigated the presence of osteocyte apoptosis in the necrotic trabeculae of the femoral head of spontaneously hypertensive rat (SHR) using the in situ nick end labeling (TUNEL) method and transmission electron microscopy. The occurrence of osteonecrosis and ossification disturbance was significantly higher in SHR compared with Wistar Kyoto (WKY) rats, and Wistar (WT) rats used as control animals (P < 0.01). A high population of TUNEL positive osteocytes was detected mainly in 10- and 15-week-old SHRs. Sectioned examination of the femoral head of SHRs and WKY rats by electron microscopy revealed apoptotic cell appearances such as aggregation of chromatin particles and lipid formation. In contrast, a positive reaction was significantly lower in osteocytes in the femoral heads of WT rats (P < 0.01). Our results indicate that apoptosis forms an important component of the global pathologic process affecting the femoral head of SHR, which leads to osteonecrosis in this region.

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    • "Kabata and his colleagues demonstrated extensive osteocyte apoptosis in a rabbit model of GC-induced ON [22]. Shibahara et al. also reported the presence of a large number of apoptotic osteocytes around necrotic areas [23]. In the present study, we observed that apoptosis occurred at the level of osteocytes, osteoblasts, and bone marrow cells in the early stages of GC-induced ON lesions in three strains of inbred rats: Wistar Kyoto, Wistar Furth and Spontaneous Hypertensive. "
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    ABSTRACT: Glucocorticoid (GC)-induced osteonecrosis (ON) is an important complication of medical therapy. The exact pathomechanisms of ON has not been clearly elucidated. There is a need for a reproducible animal model that better approximates the clinical scenario. To determine the genetic susceptibility of rats to develop GC-induced femoral head ON, we evaluated 5 different inbred strains of rats (Spontaneous Hypertensive Rat, Wistar Kyoto, Wistar Furth, SASCO Fisher and Lewis). Prednisone pellets (dosage of 1.82-2.56 mg/kg/day) were implanted subcutaneously for 90. After 90 days, the femurs were resected and examined histologically and radiographically. Pathological and histological examination was performed. Hematoxylin and eosin (H & E) staining was used to delineate the femoral head osteonecrosis lesions as well as abnormalities of articular cartilage and growth plate. The greatest differences in H & E staining were seen in the Wistar Kyoto and Wistar Furth groups. In these groups 4 out of 5 and 3 out of 5, respectively, steroid-induced rats revealed growth plate disruption with acellular areas. The TUNEL apoptosis staining assay for apoptosis revealed that 4 out of 5 of Wistar Kyoto rats, 5 out of 5 of Wistar Furth, 2 out of 4 of surviving Lewis and 2 out of 2 of the surviving spontaneous hypertensive rats had apoptotic osteocytes in trabeculae, whereas none of the Fisher rats showed apoptotic osteocytes. We postulate that Wistar Kyoto, Wistar Furth and spontaneous hypertensive rats may be strains of rats more susceptible to develop ON of the femoral head while Fisher rats were the most resistant.
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    • "Weinstein et al. reported that the number of apoptotic bone cells increased significantly in mice after steroid administration [28]. Recent studies have shown apoptotic cells in clinical and animal models of GC-induced ANFH [26,29,30]. "
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