Rousselle A V, Damiens C, Grimaud E, Fortun Y, Padrines M, Passuti N, Heymann D
Laboratory of Physiopathology of Bone Resorption, Faculty of Medicine, Nantes, France.
Histol Histopathol. 2001 Jul;16(3):727-34. doi: 10.14670/HH-16.727.
Human growth hormone (GH) has recently been found to stimulate osteoclastic resorption, cysteine-proteinase and metalloproteinase activities (MMP-2 and MMP-9) in vitro via insulin-like growth factor-I (IGF-I) produced by stromal cells. The present study investigated the effects of two extracellular matrix components (vitronectin and type-I collagen) on hGH- and hIGF-1-stimulated osteoclastic resorption and proteinase activities in a rabbit bone cell model. After 4 days of rabbit bone cell culture on dentin slices with vitronectin coating, hGH and hIGF-1 stimulated bone resorption and hIGF-1 upmodulated cysteine-proteinase activities. MMP-2 expression (but not resorption, cathepsin or MMP-9 activities) was upmodulated by hGH and hIGF-1 on dentin slices coated with type I collagen as compared to those without coating. Then, vitronectin was synergistic with hIGF-1 in the regulation of cysteine-proteinase production whereas collagen showed synergy with hGH and hIGF-1 in the regulation of MMP-2 production. Anti-alphavbeta3 totally abolished the effects of hGH and hIGF-1 on metalloproteinase release, but had no influence on cathepsin release. The results suggest that cysteine-proteinase modulation is not mediated by alphavbeta3 integrin (strongly expressed on osteoclastic surface) whereas the resorption process and metalloproteinase modulation are clearly mediated by this integrin. Our finding about the collagen coating also suggests that hGH- and hIGF-1-stimulated MMP-2 activity are mediated, along with alphavbeta3 integrin, by another adhesion molecule.
最近发现，人类生长激素（GH）可通过基质细胞产生的胰岛素样生长因子-I（IGF-I）在体外刺激破骨细胞吸收、半胱氨酸蛋白酶和金属蛋白酶活性（MMP-2和MMP-9）。本研究在兔骨细胞模型中，研究了两种细胞外基质成分（玻连蛋白和I型胶原蛋白）对hGH和hIGF-1刺激的破骨细胞吸收及蛋白酶活性的影响。在用玻连蛋白包被的牙本质切片上进行兔骨细胞培养4天后，hGH和hIGF-1刺激骨吸收，hIGF-1上调半胱氨酸蛋白酶活性。与未包被的牙本质切片相比，hGH和hIGF-1上调了包被I型胶原蛋白的牙本质切片上的MMP-2表达（但不影响吸收、组织蛋白酶或MMP-9活性）。然后，玻连蛋白在调节半胱氨酸蛋白酶产生方面与hIGF-1具有协同作用，而胶原蛋白在调节MMP-2产生方面与hGH和hIGF-1具有协同作用。抗αvβ3完全消除了hGH和hIGF-1对金属蛋白酶释放的影响，但对组织蛋白酶释放没有影响。结果表明，半胱氨酸蛋白酶调节不是由αvβ3整合素（在破骨细胞表面强烈表达）介导的，而吸收过程和金属蛋白酶调节显然是由这种整合素介导的。我们关于胶原蛋白包被的发现还表明，hGH和hIGF-1刺激的MMP-2活性除了由αvβ3整合素介导外，还由另一种粘附分子介导。
