Growth factors regulate expression of osteoblast-associated genes
Growth factors regulate expression of osteoblast-associated genes
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DOI：
10.1902/jop.1999.70.11.1345
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发表时间：
1999-11-01
影响因子：
4.3
通讯作者：
Somerman, MJ
中科院分区：
文献类型：
--
作者：
Strayhorn, CL;Garrett, JS;Somerman, MJ
背景：牙周再生治疗的目标是重建牙周组织，如骨、牙骨质和牙周韧带细胞（PDL）。建立可预测的治疗模式对这些组织的重建非常重要。本研究的目的是确定含有骨形态发生蛋白（BMPs） 2、3、4、6、7、12和13的牛骨蛋白（BP）低分子提取物单独使用或与血小板衍生生长因子（PDGF）和/或胰岛素样生长因子（IGF）联合使用对体外成骨细胞分化的影响。方法：将BP与胶原基质混合，加入到聚（dl -丙交酯-羟基乙酸酯）聚合物（PLG）中，放置在sprague - dawley大鼠颅骨的正位位置。第28天处死大鼠进行组织学分析。所有用聚合物/BP处理的位点都产生了骨，而对照位点（没有BP）没有骨形成。在确定了BP的生物活性后，我们利用小鼠骨祖细胞系MC3T3-E1细胞开始了体外研究。用Coulter计数器测定BP等生长因子对细胞增殖的影响，用Northern分析法测定特异性基因的分化程度。结果：与单独用2%血清处理的细胞相比，PDGF在10和20 ng/ml时使细胞数量增加；在这些剂量下，IGF没有产生显著影响；10、20 μ g/ml BP抑制细胞增殖。Northern分析显示，PDGF可抑制骨桥蛋白（OPN）和骨钙素（OCN）的基因表达，而BP和IGF可促进骨涎蛋白（BSP）和OPN的基因表达。BP和IGF联合使用比单独使用BP或IGF更能增强OPN的表达。PDGF能够阻断IGF对基因表达的影响，而BP不能。结论：这些结果提示BP、PDGF和IGF对细胞活性的影响不同，从而提出了联合因子增强细胞生物活性的可能性。
Background: The goal of periodontal regenerative therapies is to reconstruct periodontal tissues such as bone, cementum, and periodontal ligament cells (PDL). The need to establish predictable treatment modalities is important for reconstruction of these tissues. The aim of this study was to determine the effects of a low molecular extract of bovine bone protein (BP) containing bone morphogenetic proteins (BMPs) 2, 3, 4, 6, 7, 12, and 13, alone or in combination with platelet-derived growth factor (PDGF) and/or insulin-like growth factor (IGF) on osteoblast differentiation in vitro.Methods: BP, mixed with a collagen matrix, was added to a poly (DL-lactide-co-glycolide) polymer (PLG) and placed at orthotopic sites in the skullcaps of Sprague-Dawleys rats. At day 28, rats were sacrificed for histological analysis. All sites treated with the polymer/BP produced bone while control sites (without BP) showed no bone formation. Having established the biological activity of BP, in vitro studies were initiated using MC3T3-E1 cells, a mouse osteoprogenitor cell line. The ability of BP and other growth factors to alter cell proliferation was determined by Coulter counter, and differentiation was determined by Northern analysis for specific genes.Results: When compared with cells treated with 2% serum alone, PDGF enhanced cell numbers at 10 and 20 ng/ml; IGF produced no significant effect at these doses; and BP at 10 and 20 mu g/ml decreased cell proliferation. Northern analysis revealed that PDGF blocked gene expression of osteopontin (OPN) and osteocalcin (OCN), while BP and IGF promoted gene expression of bone sialoprotein (BSP) and OPN. The combination of BP and IGF enhanced expression of OPN beyond that of either BP or IGF alone. PDGF was able to block the effects of IGF on gene expression, but not those of BP.Conclusions: These results indicate that BP, PDGF, and IGF influence cell activity differently, and thus raise the possibility that combining factors may enhance the biological activity of cells.