Skeletal unloading causes resistance of osteoprogenitor cells to parathyroid hormone and to insulin-like growth factor-I
Skeletal unloading causes resistance of osteoprogenitor cells to parathyroid hormone and to insulin-like growth factor-I
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DOI：
10.1359/jbmr.1999.14.1.21
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发表时间：
1999-01-01
影响因子：
6.2
通讯作者：
Bikle, DD
中科院分区：
文献类型：
--
作者：
Kostenuik, PJ;Harris, J;Bikle, DD
骨骼肌去负荷降低了体内骨形成和成骨细胞的数量，并降低了体外骨髓骨祖细胞（BMOp）的数量和增殖。我们通过用间歇性甲状旁腺激素（1-34）治疗Sprague道利大鼠（n = 32）来测试甲状旁腺激素（PTH）刺激体内BMOp细胞的能力。（以8 μ g/100 g体重1小时/天），或在7天的正常负重或后肢卸载期间通过渗透微型泵与载体一起，从股骨中推出骨髓细胞并以相同的初始密度培养长达21天，正常负荷大鼠的PTH治疗引起BMOp细胞数量增加2.5倍，碱性磷酸酶（ALP）活性和矿化增加相似，与溶剂治疗大鼠的培养物相比，后肢未负荷大鼠的PTH治疗未能刺激BMOp细胞数量、ALP活性或矿化。后肢去负荷对胫骨PTH受体mRNA或蛋白水平无显著影响。从正常负荷骨中分离的BMOp细胞在体外直接PTH刺激不能刺激其增殖并抑制其分化，这表明间歇性PTH对BMOp细胞的体内合成代谢作用是由PTH诱导因子间接介导的，我们假设该因子是胰岛素样生长因子-I（IGF-I），其刺激分离自正常负载骨而非未负载骨的BMOp细胞的体外增殖和分化，这些结果表明，IGF-I介导PTH刺激正常负荷骨中BMOp细胞增殖的能力，以及未负载骨中的BMOp细胞由于其对IGF-I的抗性而对间歇性PTH治疗的合成代谢作用具有抗性。
Skeletal unloading decreases bone formation and osteoblast number in vivo and decreases the number and proliferation of bone marrow osteoprogenitor (BMOp) cells in vitro, We tested the ability of parathyroid hormone (PTH) to stimulate BMOp cells in vivo by treating Sprague Dawley rats (n = 32) with intermittent PTH(1-34) (1 h/day at 8 mu g/100 g of body weight), or with vehicle via osmotic minipumps during 7 days of normal weight bearing or hind limb unloading, Marrow cells were pushed from the femur and cultured at the same initial density for up to 21 days, PTH treatment of normally loaded rats caused a 2.5-fold increase in the number of BMOp cells, with similar increases in alkaline phosphatase (ALP) activity and mineralization, compared,vith cultures from vehicle-treated rats, PTH treatment of hind limb unloaded rats failed to stimulate BMOp cell number, ALP activity, or mineralization. Hind limb unloading had no significant effect on PTH receptor mRNA or protein levels in the tibia. Direct in vitro PTH challenge of BMOp cells isolated from normally loaded bone failed to stimulate their proliferation and inhibited their differentiation, suggesting that the in vivo anabolic effect of intermittent PTH on BMOp cells was mediated indirectly by a PTH-induced factor, We hypothesize that this factor is insulin-like growth factor-I (IGF-I), which stimulated the in vitro proliferation and differentiation of BMOp cells isolated from normally loaded bone, but not from unloaded bone, These results suggest that IGF-I mediates the ability of PTH to stimulate BMOp cell proliferation in normally loaded bone, and that BMOp cells in unloaded bone are resistant to the anabolic effect of intermittent PTH therapy due to their resistance to IGF-I.