OSTEOGENIC PROTEIN-1 STIMULATES PROLIFERATION AND DIFFERENTIATION OF HUMAN BONE-CELLS IN-VITRO

OSTEOGENIC PROTEIN-1 STIMULATES PROLIFERATION AND DIFFERENTIATION OF HUMAN BONE-CELLS IN-VITRO
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DOI:
10.1006/bbrc.1993.1973
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发表时间:
1993-08-16
影响因子:
3.1
通讯作者:
MOHAN, S
MOHAN, S
中科院分区:
生物学4区
文献类型:
--
作者:
KNUTSEN, R;WERGEDAL, JE;MOHAN, S

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使用培养的人骨细胞研究重组人成骨蛋白-1 (OP-1) 对增殖和碱性磷酸酶 (ALP) 活性的影响。使用TE85、具有成骨细胞特征的骨肉瘤细胞和源自下颌骨(HBM)的正常骨细胞。 OP-1在TE85(3-10ng/ml下是载体对照的5倍)和HBM细胞(100ng/ml下1.8倍)中以剂量依赖性方式刺激3H-胸苷掺入。在 TE85 细胞中,OP-1 还增加了细胞数量(3 ng/ml 时是载体对照的 2.4 倍)。 OP-1 刺激 TE85 细胞中的 ALP 活性(30 ng/ml 时是媒介物对照的 4 倍),但适度抑制 HBM 细胞中的 ALP 活性(100 ng/ml 时为媒介物对照的 67%)。由于 1,25(OH)2D3 已被证明可以增加许多细胞类型中的 ALP 活性,因此我们还研究了 1,25(OH)2D3 是否调节 OP-1 对 ALP 活性的影响。在 10−8M 1,25(OH)2D3 存在下,TE85 和 HBM 细胞中发生双相反应,低剂量 OP-1 刺激 ALP 活性,高剂量抑制 ALP 活性。因此,OP-1 对 ALP 活性的影响似乎受到 1,25(OH)2D3 的调节。我们的结果表明OP-1可能是成骨细胞增殖和分化的重要调节因子。
The effect of recombinant human osteogenic protein-1 (OP-1) on proliferation and alkaline phosphatase (ALP) activity was studied using human bone cells in culture. TE85, osteosarcoma cells with osteoblastic characteristics and normal bone cells derived from mandible (HBM) were used. OP-1 stimulated3H-thymidine incorporation in a dose dependent manner in TE85 (5-fold over vehicle control at 3-10 ng/ml) and HBM cells (1.8-fold at 100 ng/ml). In TE85 cells, OP-1 also increased cell number (2.4-fold over vehicle control at 3 ng/ml). OP-1 stimulated ALP activity in TE85 cells (4-fold over vehicle control at 30 ng/ml), but moderately inhibited ALP activity in HBM cells (to 67% of vehicle control at 100 ng/ml). Because 1,25(OH)2D3has been shown to increase ALP activity in many cell types, we also studied if 1,25(OH)2D3modulates the effects of OP-1 on ALP activity. In the presence of 10−8M 1,25(OH)2D3, a biphasic response occurred in TE85 and HBM cells with stimulation of ALP activity at low dose of OP-1 and inhibition at high dose. Thus, the effect of OP-1 on ALP activity appeared to be modulated by 1,25(OH)2D3. Our results suggest that OP-1 could be an important regulator of osteoblast proliferation and differentiation.