Fgf2基因敲除和杂合子小鼠对甲状旁腺激素的骨合成代谢反应受损。

Impaired bone anabolic response to parathyroid hormone in Fgf2-/- and Fgf2+/- mice.

作者信息

Hurley M M, Okada Y, Xiao L, Tanaka Y, Ito M, Okimoto N, Nakamura T, Rosen C J, Doetschman T, Coffin J D

机构信息

University of Connecticut Health Center, Farmington, CT, USA.

出版信息

Biochem Biophys Res Commun. 2006 Mar 24;341(4):989-94. doi: 10.1016/j.bbrc.2006.01.044. Epub 2006 Jan 24.

DOI:10.1016/j.bbrc.2006.01.044

PMID:16455048

Abstract

Since parathyroid hormone (PTH) increased FGF2 mRNA and protein expression in osteoblasts, and serum FGF-2 was increased in osteoporotic patients treated with PTH, we assessed whether the anabolic effect of PTH was impaired in Fgf2-/- mice. Eight-week-old Fgf2+/+ and Fgf2-/- male mice were treated with rhPTH 1-34 (80mug/kg) for 4 weeks. Micro-CT and histomorphometry demonstrated that PTH significantly increased parameters of bone formation in femurs from Fgf2+/+ mice but the changes were smaller and not significant in Fgf2-/- mice. IGF-1 was significantly reduced in serum from PTH-treated Fgf2-/- mice. DEXA analysis of femurs from Fgf2+/+, Fgf2+/-, and Fgf2-/- mice treated with rhPTH (160mug/kg) for 10 days showed that PTH significantly increased femoral BMD in Fgf2+/+ by 18%; by only 3% in Fgf2+/- mice and reduced by 3% in Fgf2-/- mice. We conclude that endogenous Fgf2 is important for maximum bone anabolic effect of PTH in mice.

摘要

由于甲状旁腺激素（PTH）可增加成骨细胞中FGF2的mRNA和蛋白表达，且接受PTH治疗的骨质疏松患者血清FGF-2水平升高，我们评估了Fgf2基因敲除小鼠中PTH的合成代谢作用是否受损。8周龄的Fgf2+/+和Fgf2-/-雄性小鼠接受重组人PTH 1-34（80μg/kg）治疗4周。显微CT和组织形态计量学结果显示，PTH显著增加了Fgf2+/+小鼠股骨的骨形成参数，但在Fgf2-/-小鼠中，这些变化较小且不显著。PTH治疗的Fgf2-/-小鼠血清中的IGF-1显著降低。对接受重组人PTH（160μg/kg）治疗10天的Fgf2+/+、Fgf2+/-和Fgf2-/-小鼠的股骨进行双能X线吸收法（DEXA）分析，结果显示，PTH使Fgf2+/+小鼠的股骨骨密度显著增加了18%；在Fgf2+/-小鼠中仅增加了3%，而在Fgf2-/-小鼠中降低了3%。我们得出结论，内源性Fgf2对小鼠中PTH的最大骨合成代谢作用至关重要。