Human TGF-β3 has been used in many studies to induce genes coding for typical cartilage matrix components and accelerate chondrogenic differentiation, making it the standard constituent in most cultivation media used for the assessment of chondrogenesis associated with various stem cell types on carrier matrices. However, in vivo data suggests that TGF-β3 and its other isoforms also induce endochondral and intramembranous osteogenesis in non-primate species to other mammals. Based on previously demonstrated improved articular cartilage induction by a using hTGF-β3 and hBMP-6 together on hADSC cultures and the interaction of TGF- β with matrix in vivo, the present study investigates the interaction of a chitosan scaffold as polyanionic polysaccharide with both growth factors. The study analyzes the difference between chondrogenic differentiation that leads to stable hyaline cartilage and the endochondral ossification route that ends in hypertrophy by extending the usual panel of investigated gene expression and stringent employment of quantitative PCR. By assessing the viability, proliferation, matrix formation and gene expression patterns it is shown that hTGF-β3 + hBMP-6 promotes improved hyaline articular cartilage formation in a chitosan scaffold in which ACAN with Col2A1 and not Col1A1 nor Col10A1 where highly expressed both at a transcriptional and translational level. Inversely, hTGF-β3 alone tended towards endochondral bone formation showing according protein and gene expression patterns. These findings demonstrate that clinical therapies should consider using hTGF-β3 + hBMP-6 in articular cartilage regeneration therapies as the synergistic interaction of these morphogens seems to ensure and maintain proper hyaline articular cartilage matrix formation counteracting degeneration to fibrous tissue or ossification. These effects are produced by interaction of the growth factors with the polysaccharide matrix.

中文翻译：

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hTGF-β3与hBMP-6的协同相互作用促进了具有hADSCs的壳聚糖支架中关节软骨的形成：对再生医学的意义。

人类TGF-β3已被用于许多研究中，以诱导编码典型软骨基质成分的基因并加速软骨形成分化，使其成为大多数用于评估与载体基质上各种干细胞相关的软骨形成的培养基中的标准成分。然而，体内数据表明，TGF-β3及其其他同工型还可以诱导其他哺乳动物在非灵长类动物体内的软骨内和膜内成骨。基于先前证明的在hADSC培养上使用hTGF-β3和hBMP-6共同改善的关节软骨诱导作用以及TGF-β与基质在体内的相互作用，本研究研究了壳聚糖支架作为聚阴离子多糖与两种生长的相互作用。因素。这项研究通过扩展通常的研究基因表达范围和严格采用定量PCR，分析了导致稳定的透明软骨的软骨形成分化与以肥大为终点的软骨内骨化途径之间的差异。通过评估生存力，增殖，基质形成和基因表达模式，表明hTGF-β3+ hBMP-6促进壳聚糖支架中透明的关节软骨形成，其中ACAN与Col2A1而不是Col1A1或Col10A1在ACAN上都高度表达转录和翻译水平。相反，单独的hTGF-β3趋向于软骨内骨形成，显示出根据蛋白质和基因表达模式。这些发现表明，临床疗法应考虑在关节软骨再生疗法中使用hTGF-β3+ hBMP-6，因为这些形态发生因子的协同相互作用似乎可以确保并维持适当的透明关节软骨基质形成，从而抵消纤维组织变性或骨化。这些作用是通过生长因子与多糖基质的相互作用产生的。