首页> 外文期刊>Journal of bone and mineral research: the official journal of the American Society for Bone and Mineral Research >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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Induction of human osteoprogenitor chemotaxis, proliferation, differentiation, and bone formation by osteoblast stimulating factor-1/pleiotrophin: osteoconductive biomimetic scaffolds for tissue engineering.

机译:成骨细胞刺激因子-1 /促卵磷脂诱导人骨祖细胞趋化,增殖,分化和骨形成:用于组织工程的骨传导仿生支架。

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摘要

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 microg/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.
机译:骨生长,再生和重塑的过程部分由直接的细胞基质环境介导。成骨细胞刺激因子1(OSF-1),通常称为多卵磷脂(PTN),是细胞外基质相关蛋白,存在于基质中,作为新骨沉积的靶标。然而,PTN对人骨祖细胞的作用仍然未知。我们在体外检查了PTN对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,尤其是在体内吸附了PTN的三维可生物降解多孔支架上的生长和分化。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-乙醇酸)(PLGA; 75:25)多孔支架上培养原代人骨髓细胞在基础和成骨条件下。仅在使用超临界流体混合方法产生的PLGA支架上观察到微不足道的细胞生长。 PTN(50微克/毫升)对人骨祖细胞具有趋化性,与对照培养物相比,浓度低至10 pg / ml时,可刺激总菌落形成,碱性磷酸酶阳性菌落形成和碱性磷酸酶特异性活性。影响是时间依赖性的。通过免疫细胞化学和原位杂交观察PTN吸附的三维支架上的碱性磷酸酶活性,I型胶原蛋白的形成以及cbfa-1,骨钙素和PTN的合成。吸附PTN的构建体在皮下植入后以及植入无胸腺小鼠的扩散室内均显示出新的骨基质和软骨形成的形态学证据。总而言之,PTN具有促进人类骨祖细胞粘附,迁移,扩展和分化的能力,这些结果表明了开发用于骨骼修复的新骨形成方案的潜力,该方案利用细胞-基质相互作用。

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