Wong M M, Rao L G, Ly H, Hamilton L, Ish-Shalom S, Sturtridge W, Tong J, McBroom R, Josse R G, Murray T M
Department of Medicine, St. Michael's Hospital, Toronto, Ontario, Canada.
Osteoporos Int. 1994 Jan;4(1):21-31. doi: 10.1007/BF02352257.
We have examined bone cells derived from iliac crest trabecular explants of 30 patients with idiopathic osteoporosis and 45 control subjects in order to determine whether intrinsic abnormalities in osteoblast function may contribute to the decreased bone formation observed in this disease. Bone cells isolated from all subjects expressed several in vitro characteristics of the osteoblast phenotype including adenylate cyclase responsiveness to parathyroid hormone (PTH) and prostaglandin E1 (PGE1), basal and 1,25(OH)2D3-stimulated alkaline phosphatase activity and osteocalcin production. Results were compared amongst three subject groups; young controls less than 40 years old, older controls over 40 years old, and osteoporotics. Osteoporotic cells were found in general to be fully active in vitro. There were no differences between osteoporotic and control cells in their basal levels of adenylate cyclase, or alkaline phosphatase, in their growth rates, or cell morphology. The cyclic AMP (cAMP) response to PTH was significantly lower in osteoporotic cells (71%, p < 0.01) and older control cells (64%, p < 0.005) relative to the response in cells from younger controls, suggesting that the decreased responsiveness in osteoporotic cells was due to subject age rather than the osteoporotic state. At the same time, the cAMP responses to PGE1 and cholera toxin were similar in cells from all three subject groups. The response to forskolin was reduced to about 40% in osteoporotic cells compared with controls, but this was not mirrored by similar differences in the responses to PTH, PGE1 or cholera toxin, suggesting that the availability of catalytic subunits is not rate-limiting in these cells. 1,25(OH)2D3-stimulated osteocalcin production was 220% higher in osteoporotics than in older controls, but the numbers tested were small and the difference did not reach significance. The one significant abnormality we observed in osteoporotic cells was in alkaline phosphatase activity: 1,25(OH)2D3-stimulated alkaline phosphatase activity was twofold higher in osteoporotics than in younger (p < 0.05), older (p < 0.05) and pooled controls (p < 0.025). The significance of this finding is unknown, but we postulate that it may reflect an intrinsic abnormality in osteoblast function in patients with idiopathic osteoporosis.
我们检测了30例特发性骨质疏松症患者和45例对照者髂嵴小梁外植体来源的骨细胞，以确定成骨细胞功能的内在异常是否可能导致该疾病中观察到的骨形成减少。从所有受试者分离的骨细胞均表现出成骨细胞表型的几种体外特征，包括腺苷酸环化酶对甲状旁腺激素（PTH）和前列腺素E1（PGE1）的反应性、基础及1,25(OH)2D3刺激的碱性磷酸酶活性和骨钙素产生。结果在三个受试者组中进行比较：年龄小于40岁的年轻对照组、年龄大于40岁的老年对照组和骨质疏松症患者组。一般发现骨质疏松症患者的细胞在体外完全活跃。骨质疏松症患者的细胞与对照细胞在腺苷酸环化酶或碱性磷酸酶的基础水平、生长速率或细胞形态方面没有差异。相对于年轻对照组细胞的反应，骨质疏松症患者细胞（71%，p<0.01）和老年对照细胞（64%）对PTH的环磷酸腺苷（cAMP）反应显著降低，这表明骨质疏松症患者细胞反应性降低是由于受试者年龄而非骨质疏松状态。同时，来自所有三个受试者组的细胞对PGE1和霍乱毒素的cAMP反应相似。与对照相比，骨质疏松症患者细胞对福斯高林的反应降低至约40%，但对PTH、PGE1或霍乱毒素的反应没有类似差异，这表明催化亚基的可用性在这些细胞中不是限速因素。骨质疏松症患者中1,25(OH)2D3刺激的骨钙素产生比老年对照组高220%，但检测数量较少，差异未达到显著水平。我们在骨质疏松症患者细胞中观察到的一个显著异常是碱性磷酸酶活性：1,25(OH)2D3刺激的碱性磷酸酶活性在骨质疏松症患者中比年轻对照组（p<0.05）、老年对照组（p<0.05）和合并对照组（p<0.025）高两倍。这一发现的意义尚不清楚，但我们推测它可能反映了特发性骨质疏松症患者成骨细胞功能的内在异常。
