Inhibition of osteoblastogenesis and promotion of apoptosis of osteoblasts and osteocytes by glucocorticoids - Potential mechanisms of their deleterious effects on bone
Inhibition of osteoblastogenesis and promotion of apoptosis of osteoblasts and osteocytes by glucocorticoids - Potential mechanisms of their deleterious effects on bone
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DOI：
10.1172/jci2799
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发表时间：
1998-07-15
影响因子：
15.9
通讯作者：
Manolagas, SC
中科院分区：
文献类型：
--
作者：
Weinstein, RS;Jilka, RL;Manolagas, SC
糖皮质激素诱导的骨疾病的特征是骨形成减少和骨孤立段的原位死亡（骨坏死），这表明糖皮质激素过量（骨质疏松症的第三大常见原因）可能影响骨细胞的出生或死亡率，从而减少其数量。为了验证这一假设，我们给7个月大的小鼠服用泼尼松龙27天，发现骨密度、血清骨钙素和松质骨面积沿着骨小梁狭窄降低。这些变化伴随着减少骨形成和营业额，确定四环素标记的椎骨，和受损的成骨细胞和破骨细胞生成，确定体外骨髓细胞培养的组织形态学分析。此外，小鼠椎骨中的成骨细胞凋亡增加了三倍，干骺端皮质骨中28%的骨细胞出现凋亡。在小鼠中，糖皮质激素诱导的骨质疏松症患者成骨细胞和骨细胞凋亡增加。破骨细胞产生减少解释了骨转换的减少，而成骨细胞产生减少和凋亡则解释了骨形成和骨小梁宽度的下降。此外，凋亡骨细胞的积累可能有助于骨坏死，这些发现提供了证据，糖皮质激素诱导的骨疾病是由于骨细胞数量的变化。
Glucocorticoid-induced bone disease is characterized by decreased bone formation and in situ death of isolated segments of bone (osteonecrosis) suggesting that glucocorticoid excess, the third most common cause of osteoporosis, may affect the birth or death rate of bone cells, thus reducing their numbers. To test this hypothesis, we administered prednisolone to 7-mo-old mice for 27 d and found decreased bone density, serum osteocalcin, and cancellous bone area along with trabecular narrowing. These changes were accompanied by diminished bone formation and turnover, as determined by histomorphometric analysis of tetracycline-labeled vertebrae, and impaired osteoblastogenesis and osteoclastogenesis, as determined by ex vivo bone marrow cell cultures. In addition, the mice exhibited a threefold increase in osteoblast apoptosis in vertebrae and showed apoptosis in 28% of the osteocytes in metaphyseal cortical bone. As in mice, an increase in osteoblast and osteocyte apoptosis was documented in patients with glucocorticoid-induced osteoporosis. Decreased production of osteoclasts explains the reduction in bone turnover, whereas decreased production and apoptosis of osteoblasts would account for the decline in bone formation and trabecular width. Furthermore, accumulation of apoptotic osteocytes may contribute to osteonecrosis, These findings provide evidence that glucocorticoid-induced bone disease arises from changes in the numbers of bone cells.