Comparison of bone morphogenetic protein-2 and osteoactivin for mesenchymal cell differentiation: effects of bolus and continuous administration.
Comparison of bone morphogenetic protein-2 and osteoactivin for mesenchymal cell differentiation: effects of bolus and continuous administration.
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DOI：
10.1002/jcp.22639
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发表时间：
2011-11
影响因子：
5.6
通讯作者：
Safadi, Fayez F.
中科院分区：
文献类型：
--
作者：
Arosarena, Oneida A.;Del Carpio-Cano, Fabiola E.;Dela Cadena, Raul A.;Rico, Mario C.;Nwodim, Emeka;Safadi, Fayez F.
目前的骨诱导蛋白治疗利用大剂量骨形态发生蛋白（BMP）的推注给药，这是昂贵的，并且可能无法复制正常的骨愈合。骨形态发生蛋白有限的体内生物活性需要研究可能增强这种活性的生长因子。在这项研究中，我们利用C3 H10 T1/2小鼠间充质干细胞系来测试骨激活素（OA）具有与骨形态发生蛋白-2（BMP-2）相当的骨诱导作用的假设，并且与推注给药相比，持续给予任一生长因子将导致成骨细胞分化增加。设计了缓释型生物可降解水凝胶，并将C3 H10 T1/2细胞生长在负载有BMP-2或OA的水凝胶上。对照在未负载的水凝胶上生长，阳性对照暴露于推注生长因子施用。在几个时间点收获细胞以评估成骨细胞分化。碱性磷酸酶（ALP）染色和活性，以及ALP和骨钙素的基因表达进行了评估。用OA或BMP-2治疗导致对成骨细胞标志物表达的类似作用。然而，在水凝胶上生长的细胞表现出成骨细胞分化，其不如用推注给药处理的细胞那样稳健。该研究表明，使用推注给药和连续释放，OA对成骨细胞分化具有与BMP-2相当的作用，并且OA的推注给药比使用水凝胶持续释放的给药具有更深远的作用。这项研究将导致更好地了解适当的交付方法的成骨生长因子，如骨关节炎修复骨折和节段性骨缺损。
Current osteoinductive protein therapy utilizes bolus administration of large doses of bone morphogenetic proteins (BMPs), which is costly, and may not replicate normal bone healing. The limited in vivo biologic activity of BMPs requires the investigation of growth factors that may enhance this activity. In this study, we utilized the C3H10T1/2 murine mesenchymal stem cell line to test the hypotheses that osteoactivin (OA) has comparable osteoinductive effects to bone morphogenetic protein-2 (BMP-2), and that sustained administration of either growth factor would result in increased osteoblastic differentiation as compared to bolus administration. Sustained release biodegradable hydrogels were designed, and C3H10T1/2 cells were grown on hydrogels loaded with BMP-2 or OA. Controls were grown on unloaded hydrogels, and positive controls were exposed to bolus growth factor administration. Cells were harvested at several time points to assess osteoblastic differentiation. Alkaline phosphatase (ALP) staining and activity, and gene expression of ALP and osteocalcin were assessed. Treatment with OA or BMP-2 resulted in comparable effects on osteoblastic marker expression. However, cells grown on hydrogels demonstrated osteoblastic differentiation that was not as robust as cells treated with bolus administration. This study shows that OA has comparable effects to BMP-2 on osteoblastic differentiation using both bolus administration and continuous release, and that bolus administration of OA has a more profound effect than administration using hydrogels for sustained release. This study will lead to a better understanding of appropriate delivery methods of osteogenic growth factors like OA for repair of fractures and segmental bone defects.
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影响因子：
5.6
作者：
Abdelmagid, Samir M.;Barbe, Mary F.;Safadi, Fayez F.
通讯作者：
Safadi, Fayez F.
影响因子：
2.9
作者：
Brunberg E;Andersson L;Cothran G;Sandberg K;Mikko S;Lindgren G
通讯作者：
Lindgren G
DOI：
10.1006/bbrc.1995.1712
发表时间：
1995-05-25
影响因子：
3.1
作者：
AONO, A;HAZAMA, M;FUJISAWA, Y
通讯作者：
FUJISAWA, Y
影响因子：
30.8
作者：
Anderson, MG;Smith, RS;John, SWM
通讯作者：
John, SWM
影响因子：
4.3
作者：
BLOM, S;HOLMSTRUP, P;DABELSTEEN, E
通讯作者：
DABELSTEEN, E