Postnatal growth and bone mass in mice with IGF-I haploinsufficiency
Postnatal growth and bone mass in mice with IGF-I haploinsufficiency
复制标题
DOI：
10.1016/j.bone.2005.11.021
复制
发表时间：
2006-06-01
期刊：
影响因子：
4.1
通讯作者：
Kream, Barbara E.
中科院分区：
文献类型：
--
作者：
He, Jianing;Rosen, Clifford J.;Kream, Barbara E.
我们检测了IGFI杂合基因敲除(NET)小鼠IGF-I单倍体不足对生长、骨量和成骨细胞分化的影响。对CD-1近交系雄性和雌性野生型(WT)和HET小鼠在1、2、4、8、12、15和18月龄时的体重、血清IGF-I和骨形态计量学进行了分析。与WT小鼠相比，HET小鼠在所有年龄段和性别中的血清IGF-I水平都降低了20%-30%。雌性HET小鼠在15个月龄前体重(10-20%)、股骨长度(4-6%)和股骨骨密度(BMD)(7-12%)显著降低。雄性HET小鼠在2个月及以后的所有参数均有显著差异。在8个月和12个月时，WT小鼠也显示出显著的性别效应：尽管雌性小鼠体重较低，但与雄性小鼠相比，雌性小鼠的股骨骨密度和股骨长度更高。显微计算机断层扫描显示8月龄HET小鼠无论性别，皮质骨面积(7-20%)和骨膜周长(5-13%)显著减少，骨小梁测量没有一致的变化模式。HET原代成骨细胞培养显示IGF-I蛋白表达减少40%，IGF-I mRNA表达减少50%。HET培养的细胞生长和增殖能力下降。因此，近交系雄性和雌性小鼠的IGF-I单倍性不足导致大多数年龄的体重、股骨长度和面骨密度降低。血清IGF-I水平与体重、骨形态计量学指标呈高度正相关。这些研究表明，IGF-I是出生后生活中骨骼大小和质量的决定因素。我们推测，成骨细胞增殖受损可能与IGF-I单倍体不足小鼠的骨骼表型有关。(C)2005 Elsevier Inc.保留所有权利。
We examined the influence of IGF-I haploinsufficiency on growth, bone mass and osteoblast differentiation in IgfI heterozygous knockout (NET) mice. Cohorts of male and female wild type (WT) and HET mice in the outbred CD-1 background were analyzed at 1, 2, 4, 8, 12, 15 and 18 months of age for body weight, serum IGF-I and bone morphometry. Compared to WT mice, HET mice had 20-30% lower serum IGF-I levels in both genders and in all age groups. Female HET mice showed significant reductions in body weight (10-20%), femur length (4-6%) and femoral bone mineral density (BMD) (7-12%) before 15 months of age. Male HET mice showed significant differences in all parameters at 2 months and thereafter. At 8 and 12 months, WT mice also showed a significant gender effect: despite their lower body weight, female mice had higher femoral BMD and femur length compared to males. Microcomputed tomography showed a significant reduction in cortical bone area (7-20%) and periosteal circumference (5-13%) with no consistent pattern of change in trabecular bone measurements in land 8-month old HET mice in both genders. HET primary osteoblast cultures showed a 40% reduction in IGF-I protein expression and a 50% decrease in IGF-I mRNA expression. Cell growth and proliferation were decreased in HET cultures. Thus, IGF-I haploinsufficiency in outbred male and female mice resulted in reduced body weight, femur length and areal BMD at most ages. Serum IGF-I levels showed a high level of positive correlation with body weight and skeletal morphometry. These studies show that IGF-I is a determinant of bone size and mass in postnatal life. We speculate that impaired osteoblast proliferation may contribute to the skeletal phenotype of mice with IGF-I haploinsufficiency. (c) 2005 Elsevier Inc. All rights reserved.