INSULIN-LIKE GROWTH FACTOR-I INCREASES TRABECULAR BONE-FORMATION AND OSTEOBLASTIC CELL-PROLIFERATION IN UNLOADED RATS

被引:125
作者
MACHWATE, M
ZERATH, E
HOLY, X
PASTOUREAU, P
MARIE, PJ
机构
[1] INSERM,U349,F-75010 PARIS,FRANCE
[2] INST RECH SERVIER,SURESNES,FRANCE
[3] CTR ETUD & RECH MED AEROSP,DIV HISTOPHYSIOL,BRETIGNY SUR ORGE,FRANCE
关键词
D O I
10.1210/en.134.3.1031
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
We previously found that the inhibition of bone formation and trabecular osteopenia induced by skeletal unloading in rats are associated with reduced proliferation of osteoblastic cells lining the bone surface. In this study, we examined the effects of insulin-like growth factor-I (IGF-I) on trabecular bone formation, bone mineral density, and proliferation of marrow-derived osteoblastic cells in unloaded rats. Skeletal unloading of hind limbs was induced by tail suspension, and recombinant human IGF-I was administered at two different doses (1.3 or 2.0 mg/kg day) in control and unloaded rats by continuous infusion for 14 days. Treatment with IGF-I had no effect on plasma glucose levels, body weight, or longitudinal bone growth. The double calcein-labeled surface, bone formation rate, and trabecular number measured at the tibial metaphysis were lower in unloaded rats compared to controls and were increased after IGF-I treatment. The increased number of bone-forming sites induced by IGF-I was associated with to the beneficial effects of IGF-I on bone formation and bone mineral content in unloaded rats, IGF-I had no effect in control rats. To evaluate the cellular mechanisms of action of IGF-I, marrow stromal cells were derived from the tibia of unloaded and control rats and studied in vitro. Unloading was associated with a decreased proliferation of alkaline phosphatase-positive (ALP+) marrow stromal cells. Treatment with IGF-I increased the number of ALP+ cells in unloaded rats, but not in control rats. IGF-I treatment increased ALP activity and osteocalcin production by marrow-derived cells in suspended and control rats, suggesting that IGF-I stimulated the proliferation and differentiation of osteoblast precursor cells. These results indicate that IGF-I infusion enhanced the recruitment of osteoblastic cells, increased trabecular bone formation, and partially prevented trabecular bone loss in unloaded rats, which supports the hypothesis that IGF-I may mediate in part the effects of loading on bone formation.
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页码:1031 / 1038
页数:8
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