Induction of Human Osteoprogenitor Chemotaxis, Proliferation, Differentiation, and Bone Formation by Osteoblast Stimulating Factor‐1/Pleiotrophin: Osteoconductive Biomimetic Scaffolds for Tissue Engineering
Induction of Human Osteoprogenitor Chemotaxis, Proliferation, Differentiation, and Bone Formation by Osteoblast Stimulating Factor‐1/Pleiotrophin: Osteoconductive Biomimetic Scaffolds for Tissue Engineering
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DOI：
10.1359/jbmr.2003.18.1.47
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发表时间：
2003-01
影响因子：
6.2
通讯作者：
Xuebin B. Yang;Rahul S. Tare;K. Partridge;H. Roach;Nicholas MP Clarke;S. Howdle;K. Shakesheff;R. Oreffo
中科院分区：
文献类型：
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作者：
Xuebin B. Yang;Rahul S. Tare;K. Partridge;H. Roach;Nicholas MP Clarke;S. Howdle;K. Shakesheff;R. Oreffo
骨生长、再生和重塑的过程部分由直接细胞基质环境介导。成骨细胞刺激因子-1（OSF-1），通常称为多效生长因子（PTN），是一种细胞外基质相关蛋白，存在于基质中，作为新骨沉积的靶点。然而，PTN对人骨祖细胞的作用仍然未知。我们研究了PTN对体外原代人骨髓基质细胞趋化性、分化和集落形成（集落形成单位-成纤维细胞）的影响，特别是对体内吸附PTN的三维可生物降解多孔支架上的生长和分化的影响。在基础和成骨条件下，在添加或不添加重组人PTN（1 pg-50 ng/ml）的组织培养塑料或聚（DL-乳酸-共-乙醇酸）（PLGA; 75：25）多孔支架上培养原代人骨髓细胞。在使用超临界流体混合方法生成的单独PLGA支架上观察到可忽略的细胞生长。与对照培养物相比，PTN（50 μg/ml）对人骨祖细胞具有趋化性，并在低至10 pg/ml的浓度下刺激总集落形成、碱性磷酸酶阳性集落形成和碱性磷酸酶比活性。效果是时间依赖性的在吸附PTN的三维支架上，通过免疫细胞化学和原位杂交观察碱性磷酸酶活性、I型胶原形成以及cbfa-1、骨钙素和PTN的合成。PTN吸附的构建体在皮下植入后以及在植入无胸腺小鼠的扩散室内显示出新骨基质和软骨形成的形态学证据。总之，PTN具有促进人骨祖细胞粘附、迁移、扩增和分化的能力，这些结果表明开发利用细胞-基质相互作用的从头骨形成用于骨骼修复的方案的潜力。
The process of bone growth, regeneration, and remodeling is mediated, in part, by the immediate cell‐matrix environment. Osteoblast stimulating factor‐1 (OSF‐1), more commonly known as pleiotrophin (PTN), is an extracellular matrix‐associated protein, present in matrices, which act as targets for the deposition of new bone. However, the actions of PTN on human bone progenitor cells remain unknown. We examined the effects of PTN on primary human bone marrow stromal cells chemotaxis, differentiation, and colony formation (colony forming unit‐fibroblastic) in vitro, and in particular, growth and differentiation on three‐dimensional biodegradable porous scaffolds adsorbed with PTN in vivo. Primary human bone marrow cells were cultured on tissue culture plastic or poly(DL‐lactic acid‐co‐glycolic acid) (PLGA; 75:25) porous scaffolds with or without addition of recombinant human PTN (1 pg‐50 ng/ml) in basal and osteogenic conditions. Negligible cellular growth was observed on PLGA scaffold alone, generated using a super‐critical fluid mixing method. PTN (50 μg/ml) was chemotactic to human osteoprogenitors and stimulated total colony formation, alkaline phosphatase‐positive colony formation, and alkaline phosphatase‐specific activity at concentrations as low as 10 pg/ml compared with control cultures. The effects were time‐dependent. On three‐dimensional scaffolds adsorbed with PTN, alkaline phosphatase activity, type I collagen formation, and synthesis of cbfa‐1, osteocalcin, and PTN were observed by immunocytochemistry and PTN expression by in situ hybridization. PTN‐adsorbed constructs showed morphologic evidence of new bone matrix and cartilage formation after subcutaneous implantation as well as within diffusion chambers implanted into athymic mice. In summary, PTN has the ability to promote adhesion, migration, expansion, and differentiation of human osteoprogenitor cells, and these results indicate the potential to develop protocols for de novo bone formation for skeletal repair that exploit cell‐matrix interactions.