Serum IGF-1 affects skeletal acquisition in a temporal and compartment-specific manner.
Serum IGF-1 affects skeletal acquisition in a temporal and compartment-specific manner.
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DOI：
10.1371/journal.pone.0014762
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发表时间：
2011-03-18
期刊：
影响因子：
3.7
通讯作者：
Yakar S
中科院分区：
文献类型：
--
作者：
Courtland HW;Elis S;Wu Y;Sun H;Rosen CJ;Jepsen KJ;Yakar S
胰岛素样生长因子-1 (IGF-1) 通过建立纵向和横向骨增长，在骨骼生长发育中发挥着关键作用。 IGF-1 还与成年晚期和衰老过程中骨量的维持有关，因为血清 IGF-1 水平的降低似乎与骨矿物质密度 (BMD) 的降低相关。尽管信息丰富，但迄今为止，小鼠模型还无法区分 IGF-1 缺失对骨骼发育的时间影响。为了解决这个问题，我们对诱导型 LID 小鼠 (iLID) 进行了骨骼表征，其中血清 IGF-1 水平在选定的年龄被耗尽。我们发现，雄性 iLID 小鼠在成年前（4 周）消除血清 IGF-1 会降低小梁骨结构，并在 16 周（成年期）显着降低横向皮质骨特性（Ct.Ar、Ct.Th）。同样，iLID 雄性在 8 周龄时血清 IGF-1 的消耗导致 32 周（成年晚期）横向皮质骨特性（Ct.Ar、Ct.Th）显着降低，但对小梁骨结构没有影响。相比之下，在骨获取高峰（第 16 周）后血清 IGF-1 的消耗导致小梁骨结构增强，但与对照组相比，到 32 周时皮质骨特性没有显着变化。这些结果表明，虽然血清 IGF-1 对于出生后生长阶段的骨生成至关重要，但在骨获取高峰（16 周）后 IGF-1 的消耗是区室特异性的，并且不会对老年小鼠的皮质骨量产生不利影响。
Insulin-like growth factor-1 (IGF-1) plays a critical role in the development of the growing skeleton by establishing both longitudinal and transverse bone accrual. IGF-1 has also been implicated in the maintenance of bone mass during late adulthood and aging, as decreases in serum IGF-1 levels appear to correlate with decreases in bone mineral density (BMD). Although informative, mouse models to date have been unable to separate the temporal effects of IGF-1 depletion on skeletal development. To address this problem, we performed a skeletal characterization of the inducible LID mouse (iLID), in which serum IGF-1 levels are depleted at selected ages. We found that depletion of serum IGF-1 in male iLID mice prior to adulthood (4 weeks) decreased trabecular bone architecture and significantly reduced transverse cortical bone properties (Ct.Ar, Ct.Th) by 16 weeks (adulthood). Likewise, depletion of serum IGF-1 in iLID males at 8 weeks of age, resulted in significantly reduced transverse cortical bone properties (Ct.Ar, Ct.Th) by 32 weeks (late adulthood), but had no effect on trabecular bone architecture. In contrast, depletion of serum IGF-1 after peak bone acquisition (at 16 weeks) resulted in enhancement of trabecular bone architecture, but no significant changes in cortical bone properties by 32 weeks as compared to controls. These results indicate that while serum IGF-1 is essential for bone accrual during the postnatal growth phase, depletion of IGF-1 after peak bone acquisition (16 weeks) is compartment-specific and does not have a detrimental effect on cortical bone mass in the older adult mouse.
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