Raisz L G, Simmons H A, Hansen C T
Metab Bone Dis Relat Res. 1981;3(2):117-21. doi: 10.1016/0221-8747(81)90029-1.
We studied bone resorption in rats bearing the ia and tl osteopetrotic mutant genes by measuring the release of previously incorporated 45Ca from the long bone shafts of 19-day fetuses. Fetuses from matings of ia/ia to ia/+ rats showed good bone resorptive responses. There was a significant increase in 45Ca release in control cultures compared to killed bones, with further stimulation by parathyroid hormone (PTH) and no bimodal distribution. Fetuses from matings of ia/ia rats to ia/ia rats showed similar resorptive responses. The responses were greater in media supplemented with serum than in media containing bovine serum albumin. Serum from ia/ia rats did not inhibit resorption of ia/ia or normal bones. In contrast, matings of tl/+ to tl/+ heterozygotes produced 18 of 71 fetuses which showed markedly decreased bone resorptive responses and were therefore considered to be tl/tl. These "non-responders" showed no significant cell-mediated control resorption compared with killed bones and no response to PTH, 1,25-dihydroxyvitamin D or prostaglandin E2. The remaining animals, which were presumptive heterozygotes or homozygous normals, showed significant control resorption and responded with further increases to all three stimulators. Morphologically the tibiae from the fetuses of non-responders were not grossly abnormal, but lacked typical multinucleated osteoclasts. Osteoclasts were found in most samples from responsive fetuses.
我们通过测量19天龄胎儿长骨干中先前掺入的45Ca的释放，研究了携带ia和tl骨石化突变基因的大鼠的骨吸收情况。ia/ia与ia/+大鼠交配所产胎儿表现出良好的骨吸收反应。与处死的骨骼相比，对照培养物中45Ca的释放显著增加，甲状旁腺激素（PTH）可进一步刺激释放，且不存在双峰分布。ia/ia大鼠与ia/ia大鼠交配所产胎儿表现出相似的吸收反应。在补充血清的培养基中的反应比含有牛血清白蛋白的培养基中的反应更大。ia/ia大鼠的血清不抑制ia/ia或正常骨骼的吸收。相比之下，tl/+与tl/+杂合子交配产生的71个胎儿中有18个表现出明显降低的骨吸收反应，因此被认为是tl/tl。与处死的骨骼相比，这些“无反应者”未表现出明显的细胞介导的对照吸收，对PTH、1,25 - 二羟维生素D或前列腺素E2也无反应。其余推测为杂合子或纯合正常的动物表现出明显的对照吸收，对所有三种刺激物均有进一步增加的反应。形态学上，无反应者胎儿的胫骨无明显异常，但缺乏典型的多核破骨细胞。在大多数有反应的胎儿样本中发现了破骨细胞。
