IGF-binding protein-5 stimulates osteoblast activity and bone accretion in ovariectomized mice

被引:45
作者
Andress, DL
机构
[1] VA Puget Sound Hlth Care Syst, Dept Med, Seattle, WA 98108 USA
[2] Univ Washington, Dept Med, Seattle, WA 98105 USA
来源
AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM | 2001年 / 281卷 / 02期
关键词
bone formation; bone mineral density; estrogen deficiency;
D O I
10.1152/ajpendo.2001.281.2.E283
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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.
引用
收藏
页码:E283 / E288
页数:6
相关论文
共 27 条
[1]   CARBOXY-TRUNCATED INSULIN-LIKE GROWTH-FACTOR BINDING PROTEIN-5 STIMULATES MITOGENESIS IN OSTEOBLAST-LIKE CELLS [J].
ANDRESS, DL ;
LOOP, SM ;
ZAPF, J ;
KIEFER, MC .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1993, 195 (01) :25-30
[2]  
ANDRESS DL, 1995, J BIOL CHEM, V270, P28289
[3]   Insulin-like growth factor-binding protein-5 (IGFBP-5) stimulates phosphorylation of the IGFBP-5 receptor [J].
Andress, DL .
AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM, 1998, 274 (04) :E744-E750
[4]   COMPARISON OF PARATHYROID-HORMONE ASSAYS WITH BONE HISTOMORPHOMETRY IN RENAL OSTEODYSTROPHY [J].
ANDRESS, DL ;
ENDRES, DB ;
MALONEY, NA ;
KOPP, JB ;
COBURN, JW ;
SHERRARD, DJ .
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 1986, 63 (05) :1163-1169
[5]  
ANDRESS DL, 1992, J BIOL CHEM, V267, P22467
[6]   A NOVEL HUMAN INSULIN-LIKE GROWTH-FACTOR BINDING-PROTEIN SECRETED BY OSTEOBLAST-LIKE CELLS [J].
ANDRESS, DL ;
BIRNBAUM, RS .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1991, 176 (01) :213-218
[7]  
BAIN SD, 1993, J BONE MINER RES, V8, P435
[8]   ISOLATION OF A NOVEL INSULIN-LIKE GROWTH-FACTOR (IGF) BINDING-PROTEIN FROM HUMAN BONE - A POTENTIAL CANDIDATE FOR FIXING IGF-II IN HUMAN BONE [J].
BAUTISTA, CM ;
BAYLINK, DJ ;
MOHAN, S .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1991, 176 (02) :756-763
[9]   ESTROGEN MAINTAINS TRABECULAR BONE VOLUME IN RATS NOT ONLY BY SUPPRESSION OF BONE-RESORPTION BUT ALSO BY STIMULATION OF BONE-FORMATION [J].
CHOW, J ;
TOBIAS, JH ;
COLSTON, KW ;
CHAMBERS, TJ .
JOURNAL OF CLINICAL INVESTIGATION, 1992, 89 (01) :74-78
[10]   MEAN WALL THICKNESS AND FORMATION PERIODS OF TRABECULAR BONE PACKETS IN IDIOPATHIC OSTEOPOROSIS [J].
DARBY, AJ ;
MEUNIER, PJ .
CALCIFIED TISSUE INTERNATIONAL, 1981, 33 (03) :199-204