Investigations of bones of transgenic mice over expressing human human osteob stimulating factor-1 (OSF-1).

我们分离了在成骨细胞中表达的成骨细胞刺激因子-1（osf-1），并建立了过表达osf-1的转基因小鼠，研究其对同位素成骨的影响。与野生型小鼠相比，osf-1过表达转基因小鼠的骨矿物质含量、骨密度和骨强度增加。切除卵巢的osf-1过表达小鼠，即雌激素缺乏引起的骨质疏松模型，保持与假手术野生型小鼠相同的骨体积，将表达纯合osf-1的雄性小鼠与野生型雌性小鼠交配，得到osf-1杂合小鼠。然后将杂合子雄鼠与杂合子雌鼠交配，得到另一窝携带或不携带osf-1基因的雌鼠。我们用108只雌性同窝仔来检查骨强度。对14周龄的小鼠进行手术，其中一半切除卵巢，另一半进行假手术。结果，我们获得了42只转基因并切除卵巢的小鼠，11只未转基因并切除卵巢的小鼠，46只转基因并假手术的小鼠，9只转基因阴性并假手术的小鼠。在28周龄时切除小鼠股骨，采用三点弯曲试验测定其全股骨的破坏载荷。支架间距为9 mm，十字头速度为0.5 mm/min。在假手术组中，与转基因小鼠和野生型小鼠相比，从失败负荷/体重的值^2/3来看，转基因小鼠的值有强于野生型小鼠的趋势。（p = 0.2175）每单位杂交的破坏载荷近似于每单位体重的破坏载荷^[2/3]。我们可以认为，骨体积增加的osf-1过表达转基因小鼠也可能增加其骨强度。

We have isolated osteoblast stimulating factor-1 (osf-1), that expressed in osteoblasts, and made transgenic mice over expressing osf-1 to investigate the effect to isotopic osteogenesis. Osf-1 over-expressing transgenic mice increased in bone mineral content, bone mineral density, and bone strength than wild type mice. Ovariectomized osf-1 over expressing mice, which are model of osteoporosis caused by estrogen deficiency, kept as the same bone volume as the sham operated wild type mice.Mating male mice expressing homozyous osf-1, with wild type female mice, we got osf-1 heterozygous littermates. Next, we mated the heterozygous male and the heterozygous female littermates, and got another littermates which had osf-1 gene or not. We used 108 female littermates to examine the bone strength. 14-week-old mice were operated, half number of them were ovariectomized and another half number of them were sham-operated. As a result, we gained 42 mice having transgene and ovariectomized, 11 mice having no transgene and ovariectomized, 46 mice having transgene and sham-operated, 9 mice being negative with transgene and sham-operated. We excised femora of these mice at the age of 28-week-old, and evaluated their failure load of whole femora by three point bending test. The span between the supprts was 9 mm long, and the cross-head-speed was 0.5 mm/min.In sham-operated mice groups, comparing with the transgenic mice and the wild type mice, by the value of failure load/body weight^2/3, the value of the transgenic mice tend to be stronger than that of the wild ones. (p=0.2175) Failure load per unit cross was approximated by that per body weight^2/3.We can suggest the posibility that osf-1 over expression transgenic mice with increasing bone volume are also increasing their bone strength.