Insulin-like growth factor regulates peak bone mineral density in mice by both growth hormone-dependent and -independent mechanisms
Insulin-like growth factor regulates peak bone mineral density in mice by both growth hormone-dependent and -independent mechanisms
复制标题
DOI：
10.1210/en.2002-220948
复制
发表时间：
2003-03-01
期刊：
影响因子：
4.8
通讯作者：
Baylink, DJ
中科院分区：
文献类型：
--
作者：
Mohan, S;Richman, C;Baylink, DJ
为了评估GH/IGF轴对峰值骨密度（BMD）发展的相对贡献，我们测量了IGF-I敲除（KO）、IGF-II敲除和GH缺陷lit/lit小鼠及其相应对照小鼠在第23天的骨骼变化。（prepubertal），31（青春期）和56（青春期后）在整个股骨的双能X线吸收测定法和中骨干外周定量计算机断层扫描。生长因子的缺乏导致不同程度的骨骼生长失败，这取决于生长期和所涉及的生长因子。在第23天，与对照小鼠相比，IGF-I、IGF-II和GH缺陷小鼠的股骨长度、大小和BMD分别减少25- 40%、15 - 17%和8- 10%。在青春期，对照小鼠的骨密度增加了40%，IGF-II KO和GH缺陷小鼠的骨密度增加了15%，而IGF-I KO小鼠的骨密度没有增加。IGF-I的破坏，而不是IGF-II，完全阻止了青春期发生的骨膜扩张，而GH缺乏小鼠减少了50%。在第56天，与对照小鼠相比，IGF-I、IGF-II和GH缺陷小鼠的股骨长度、尺寸和BMD分别减少40- 55%、11- 18%和25- 32%。我们的数据表明：1）IGF-I缺陷小鼠的骨生长受损程度大于IGF-II或GH缺陷小鼠; 2）GH/IGF-I（而非IGF-II）对青春期诱导的骨生长至关重要; 3）青春期前IGF-I对骨生长的影响主要通过不依赖于GH的机制介导，而青春期期间则通过GH依赖性和GH非依赖性机制介导。
To evaluate the relative contribution of the GH/IGF axis to the development of peak bone mineral density (BMD), we measured skeletal changes in IGF-I knockout (KO), IGF-II KO, and GH-deficient lit/lit mice and their corresponding control mice at d 23 (prepubertal), 31 (pubertal), and 56 (postpubertal) in the entire femur by dual energy x-ray absorptiometry and in the mid-diaphysis by peripheral quantitative computed tomography. Lack of growth factors resulted in different degrees of failure of skeletal growth depending on the growth period and the growth factor involved. At d 23, femoral length, size, and BMD were reduced by 25-40%,15-17%, and 8-10%, respectively, in mice deficient in IGF-I, IGF-II, and GH compared with the control mice. During puberty, BMD increased by 40% in control mice and by 15% in IGF-II KO and GH-deficient mice, whereas it did not increase in the IGF-I KO mice. Disruption of IGF-I, but not IGF-II, completely prevented the periosteal expansion that occurs during puberty, whereas it was reduced by 50% in GH-deficient mice. At d 56, femoral length, size, and BMD were reduced by 40-55%, 11-18%, and 25-32%, respectively, in mice deficient in IGF-I, IGF-II, and GH compared with the control mice. Our data demonstrate that: 1) mice deficient in IGF-I exhibit a greater impairment in bone accretion than mice deficient in IGF-II or GH; 2) GH/IGF-I, but not IGF-II, is critical for puberty-induced bone growth; and 3) IGF-I effects on bone accretion during prepuberty are mediated predominantly via mechanisms independent of GH, whereas during puberty they are mediated via both GH-dependent and GH-independent mechanisms.