Carleton Stephanie M, Whitford Gary M, Phillips Charlotte L
Department of Biochemistry, University of Missouri, Columbia, MO 65211, USA.
J Nutr. 2010 Oct;140(10):1752-6. doi: 10.3945/jn.109.120261. Epub 2010 Aug 19.
Osteogenesis imperfecta (OI) is a clinically and genetically heterogeneous disease due primarily to mutations in the type I procollagen genes, COL1A1 and COL1A2, causing bone deformity and numerous lifetime fractures. OI murine (oim) model mice carry a mutation in the col1a2 gene causing aberrant production of homotrimeric type I collagen [α1(I)(3)], leading to bone fragility and glomerular accumulation of type I collagen. Previous studies demonstrated that heterozygous (+/oim) and homozygous (oim/oim) mice have elevated tibiae fluoride concentrations but reduced femoral biomechanics. However, it is unclear whether these 2 variables are causally related, because impaired renal function could reduce urinary fluoride excretion, thus elevating bone fluoride concentrations regardless of disease status. Our goal in this study was to determine whether dietary fluoride restriction would improve femoral biomechanics in oim mice. Wild-type, +/oim, and oim/oim mice were fed a control (5 mg/kg fluoride) or fluoride-restricted diet (0 mg/kg fluoride) for ∼13 wk, at which time plasma and femora were analyzed for fluoride concentrations and bone biomechanical properties. In wild-type, +/oim, and oim/oim mice, dietary fluoride restriction reduced femoral fluoride burden by 54-74%, respectively (P < 0.05), without affecting glomerular collagen deposition. Oim/oim mice fed the fluoride-restricted diet had reduced material tensile strength (P < 0.05) compared with oim/oim mice fed the control diet. However, dietary fluoride restriction did not affect stiffness or whole bone femoral breaking strength, regardless of genotype. These data suggest that oim mice have reduced bone strength due to homotrimeric type I collagen, independent of bone fluoride content.
成骨不全症（OI）是一种临床和遗传异质性疾病，主要由于I型前胶原基因COL1A1和COL1A2发生突变，导致骨骼畸形和终生多处骨折。OI小鼠（oim）模型小鼠的col1a2基因发生突变，导致同源三聚体I型胶原蛋白[α1(I)(3)]产生异常，从而导致骨骼脆弱和I型胶原蛋白在肾小球中积聚。先前的研究表明，杂合子（+/oim）和纯合子（oim/oim）小鼠的胫骨氟浓度升高，但股骨生物力学性能降低。然而，目前尚不清楚这两个变量是否存在因果关系，因为肾功能受损可能会减少尿氟排泄，从而无论疾病状态如何都会提高骨氟浓度。我们在本研究中的目标是确定限制饮食中的氟是否会改善oim小鼠的股骨生物力学性能。野生型、+/oim和oim/oim小鼠分别喂食对照饮食（5mg/kg氟）或限氟饮食（0mg/kg氟）约13周，此时分析血浆和股骨的氟浓度以及骨生物力学性能。在野生型、+/oim和oim/oim小鼠中，限制饮食中的氟分别使股骨氟负荷降低了54-74%（P<0.05），且不影响肾小球胶原蛋白沉积。与喂食对照饮食的oim/oim小鼠相比|，喂食限氟饮食的oim/oim小鼠的材料抗张强度降低（P<0.05）。然而，无论基因型如何，限制饮食中的氟均不影响硬度或股骨整体断裂强度。这些数据表明，oim小鼠由于同源三聚体I型胶原蛋白而骨强度降低，与骨氟含量无关。
