Endoplasmic reticulum stress-induced apoptosis of osteoblasts within the osteolytic craniums / 中国组织工程研究

ABSTRACT

BACKGROUND:Wear particles-induced osteoblasts apoptosis in vitro has been documented in many studies. However, the apoptosis of osteoblasts in osteolytic bone tissue and the selective mechanisms involved in the pathogenesis of osteolysis have been studied rarely. OBJECTIVE:To investigate the influence of endoplasmic reticulum (ER) stress on the apoptosis of osteoblasts in osteolytic bone tissue and osteolysis progression. METHODS:The mouse model of osteolysis was induced with wear particles placed onto the calvaria. The experiment was divided into four groupsblank control group (PBS stimulation);wear particle group (nano-al oy powder suspension stimulation);ER stress positive control group (nano-al oy powder+thapsin stimulation);and ER stress inhibitor group (nano-al oy powder+sodium 4-phenylbutyrate stimulation). The histopathologic change of osteolysis was assessed by hematoxylin-eosin, toluidine blue and alkaline phosphatase staining. Osteoblast proliferation and differentiation in osteolytic craniums were measured. The expression of ER stress markers in osteolytic craniums was examined by western blot analysis. Osteoblast apoptosis was analyzed by TUNEL staining and immunohistochemistry of Caspase-3 in osteolytic craniums. RESULTS AND CONCLUSION:Wear particles were capable of inducing osteolysis, aggravating the infiltration of inflammatory cells, and inhibiting the differentiation of osteoblasts in osteolytic craniums. Meanwhile wear particles upregulated the ER stress markers and promote the apoptosis in osteolytic craniums. Blocking ER stress with sodium 4-phenylbutyrate dramatical y reduced the severity of osteolysis, significantly reduced bone invasion and inflammatory infiltration, promoted the differentiation of osteoblasts, and dramatical y reduced the apoptosis. Along with apoptosis, the expression of ER stress marker was decreased. The present study suggests that the ER stress may be crucial for osteolysis and represent a potential therapeutic target in the prevention and treatment of patients with total joint replacement who are at high risk of early aseptic loosening development.