Prolonged ectopic calcification induced by BMP-2-derived synthetic peptide.
Prolonged ectopic calcification induced by BMP-2-derived synthetic peptide.
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DOI：
10.1002/jbm.a.30071
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发表时间：
2004-07
期刊：
影响因子：
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通讯作者：
Atsuhiro Saito;Yoshihisa Suzuki;S. Ogata;C. Ohtsuki;M. Tanihara
中科院分区：
文献类型：
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作者：
Atsuhiro Saito;Yoshihisa Suzuki;S. Ogata;C. Ohtsuki;M. Tanihara
骨形态发生蛋白-2(BMP-2)促进骨和软骨的形成和再生，是最有前途的骨修复材料。然而，它也具有广泛的功能，如在器官发生和细胞凋亡中。因此，我们研究了一种新的与BMP-2的73-92位氨基酸残基相对应的合成肽。这种多肽与BMP-2特异性受体结合，提高了小鼠细胞系C3H10T1/2的碱性磷酸酶活性和骨钙素mRNA的表达。73-92多肽与共价交联的海藻酸凝胶结合时也能诱导异位钙化。在这里，我们报告73-92肽结合的海藻酸盐凝胶在大鼠小腿肌肉中显示出长达7周的异位钙化。相反，植入重组人骨形成蛋白-2的胶原凝胶在3周出现最大的异位钙化，5周后已形成的钙化产物消失。组织学检查显示，73-92肽海藻酸凝胶诱导了大量的成骨细胞样细胞和少量的破骨细胞。相反，植入重组人骨形成蛋白-2的胶原凝胶可诱导大量破骨细胞。这些结果表明，藻酸盐凝胶上的73-92肽在植入部位保持活性，持续诱导成骨细胞前体细胞向成骨细胞分化，并激活成骨细胞促进异位钙化。
Bone morphogenetic protein-2 (BMP-2) promotes the formation and regeneration of bone and cartilage, and therefore constitutes the most promising candidate for a bone repair material. However, it also has a wide range of functions, such as in organogenesis and apoptosis. Therefore, we investigated a novel synthetic peptide corresponding to residues 73-92 of BMP-2. This peptide bound to a BMP-2-specific receptor and elevated both alkaline phosphatase activity and osteocalcin mRNA in the murine cell line, C3H10T1/2. The 73-92 peptide also induced ectopic calcification when conjugated to a covalently crosslinked alginate gel. Here we report that the 73-92 peptide-conjugated alginate gel showed prolonged ectopic calcification for up to 7 weeks in rat calf muscle. In contrast, rhBMP-2-impregnated collagen gel showed maximum ectopic calcification at 3 weeks, and the calcified products that had formed disappeared after 5 weeks. Histological examination showed that the 73-92 peptide-conjugated alginate gel induced many osteoblast-like cells and few osteoclasts. In contrast, rhBMP-2-impregnated collagen gel induced many osteoclasts. These results suggest that the 73-92 peptide on alginate gel remains active at the implanted site, continuously induces differentiation of osteoblast precursor cells into osteoblasts, and activates osteoblasts to promote ectopic calcification.