Rifas L, Dawson L L, Halstead L R, Roberts M, Avioli L V
Division of Bone and Mineral Diseases, Washington University Medical Center, St. Louis, Missouri 63110.
Calcif Tissue Int. 1994 Jun;54(6):505-10. doi: 10.1007/BF00334333.
Human hypophophatemic vitamin D-resistant rickets (X-linked hypophosphatemia-XLH) is characterized by hypophosphatemia, a decreased tubular reabsorption of phosphate (P(i)) and defective skeleton mineralization. Utilizing a mouse model (Hyp) of XLH, which demonstrates biological abnormalities and skeletal defects of XLH, we analyzed sodium-dependent phosphate transport in isolated osteoblasts derived from the calvaria of normophosphatemic and hypophosphatemic mice. Initial rates of phosphate uptake by normal and Hyp osteoblasts showed similar slopes. Osteoblasts from both normal and Hyp mice exhibited saturable, sodium-dependent phosphate transport with apparent Vmax and Km values not significantly different (normal mice, Vmax = 24.30 +/- 3.45 nmol/mg prot. 10 min, Km = 349.49 +/- 95.20 mumol/liter; Hyp mice, Vmax = 23.03 +/- 3.41 nmol/mg prot. 10 min, Km = 453.64 +/- 106.93 mumol/liter, n = 24). No differences were found in the ability of normal and Hyp osteoblasts to respond to P(i) transport after 5 hours of P(i) deprivation. Both cell types exhibited a similar increase in cAMP in response to PTH. The accumulated results demonstrate that P(i) uptake and transport in normal and Hyp mouse osteoblasts is a sodium-dependent saturable process. As osteoblast P(i) uptake and transport is apparently normal in the Hyp mouse model of XLH, the "osteoblastic failure" described for the Hyp mouse should be attributed to other mechanism(s).
人类低磷性维生素D抵抗性佝偻病（X连锁低磷血症-XLH）的特征为低磷血症、肾小管对磷酸盐（P(i)）重吸收减少以及骨骼矿化缺陷。利用XLH的小鼠模型（Hyp），该模型表现出XLH的生物学异常和骨骼缺陷，我们分析了来自正常磷血症和低磷血症小鼠颅骨的分离成骨细胞中钠依赖性磷酸盐转运。正常和成骨细胞（Hyp）的磷酸盐摄取初始速率显示出相似的斜率。正常和Hyp小鼠的成骨细胞均表现出可饱和的、钠依赖性磷酸盐转运，其表观Vmax和Km值无显著差异（正常小鼠，Vmax = 24.30 +/- 3.45 nmol/mg蛋白·10分钟，Km = 349.49 +/- 95.20 μmol/升；Hyp小鼠，Vmax = 23.03 +/- 3.41 nmol/mg蛋白·10分钟，Km = 453.64 +/- 106.93 μmol/升，n = 24）。在磷酸盐剥夺5小时后，正常和Hyp成骨细胞对P(i)转运的反应能力未发现差异。两种细胞类型对甲状旁腺激素（PTH）的反应均表现出cAMP的类似增加。累积结果表明，正常和Hyp小鼠成骨细胞中的P(i)摄取和转运是一个钠依赖性可饱和过程。由于在XLH的Hyp小鼠模型中，成骨细胞的P(i)摄取和转运显然正常，因此针对Hyp小鼠所描述的“成骨细胞功能衰竭”应归因于其他机制。
