IGF-binding protein-5 stimulates osteoblast activity and bone accretion in ovariectomized mice
IGF-binding protein-5 stimulates osteoblast activity and bone accretion in ovariectomized mice
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DOI：
10.1152/ajpendo.2001.281.2.e283
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发表时间：
2001-08-01
影响因子：
5.1
通讯作者：
Andress, DL
中科院分区：
文献类型：
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作者：
Andress, DL
胰岛素样生长因子结合蛋白-5(IGFBP-5)是一种成骨细胞分泌蛋白，可整合到矿化的骨基质中。在成骨细胞培养中，IGFBP-5通过不依赖于IGF的机制刺激细胞增殖。为了评价IGFBP-5是否能刺激成骨细胞活性和促进成骨细胞功能不全小鼠的骨生长，对卵巢切除(OVX)小鼠每日皮下注射完整的[IGFBP-5(完整)]和截短的IGFBP-5[IGFBP-5-(1-169)]8wk。每2周测量一次的股骨和脊柱骨密度(BMD)显示出对IGFBP-5的反应，早期和持续的增加。松质骨骨组织形态计量学显示，与去卵巢对照组相比，股骨干骺端[IGFBP-5(1-169)]和脊柱的骨形成率均显著升高。IGFBP-5还刺激了股骨和脊柱中的成骨细胞数量。这些数据表明IGFBP-5通过刺激成骨细胞活性有效地促进去卵巢小鼠的骨形成和骨生长。IGFBP-5-(1-169)在体内具有生物活性的发现表明，这种骨合成代谢作用并不需要羧基末端。
Insulin-like growth factor binding protein-5 (IGFBP-5) is an osteoblast secretory protein that becomes incorporated into the mineralized bone matrix. In osteoblast cultures, IGFBP-5 stimulates cell proliferation by an IGF-independent mechanism. To evaluate whether IGFBP-5 can stimulate osteoblast activity and enhance bone accretion in a mouse model of osteoblast insufficiency, daily subcutaneous injections of either intact [IGFBP-5 (intact)] or carboxy-truncated IGFBP-5 [IGFBP-5-(1-169)] were given to ovariectomized (OVX) mice for 8 wk. Femur and spine bone mineral density (BMD), measured every 2 wk, showed early and sustained increases in response to IGFBP-5. Bone histomorphometry of cancellous bone showed significant elevations in the bone formation rate in both the femur metaphysis [IGFBP-5(1-169)] only) and spine compared with OVX controls. IGFBP-5 also stimulated osteoblast number in the femur IGFBP-5-( 1-169) only) and spine. These data indicate that IGFBP-5 effectively enhances bone formation and bone accretion in OVX mice by stimulating osteoblast activity. The finding that IGFBP-5-(1-169) is bioactive in vivo indicates that the carboxy-terminal portion is not required for this bone anabolic effect.