Liu Lei, Miao Yali, Shi Xuetao, Gao Huichang, Wang Yingjun
School of Material Science and Engineering, South China University of Technology, Guangzhou 510640, P. R. China.
National Engineering Research Center for Tissue Restoration and Reconstruction, South China University of Technology, Guangzhou 510006, P. R. China.
ACS Biomater Sci Eng. 2020 Mar 9;6(3):1500-1509. doi: 10.1021/acsbiomaterials.9b01374. Epub 2020 Feb 25.
Phosphorous-containing biopolymers have been applied to expedite the regeneration of damaged bone tissue by stimulating the function of phosphorous groups in natural bones. However, the underlying mechanism of phosphorous-containing biopolymers in promoting osteogenic differentiation is unclarified. Herein, we synthesized phosphorylated chitosan hydrogels by incorporating phosphocreatine into chitosan molecular chains under mild conditions. The introduction of phosphate groups improved properties of protein adsorption and calcium deposition without affecting the morphology of hydrogels. Our results showed that phosphorylated chitosan hydrogels could not only promote alkaline phosphatase activity and mineralization but also upregulate the expression of osteogenic-related genes and proteins. Meanwhile, application of c-Jun N-terminal kinase inhibitor SP600125 and p38 mitogen-activated protein kinase inhibitor SB203580 repressed the expression of osteogenic-related markers in gene and protein levels. To the best of our knowledge, it is reported for the first time that phosphorous-containing biopolymers promote osteogenic differentiation of osteoblasts via JNK and p38 signaling pathways.
含磷生物聚合物已被应用于通过刺激天然骨骼中磷基团的功能来加速受损骨组织的再生。然而，含磷生物聚合物促进成骨细胞分化的潜在机制尚不清楚。在此，我们在温和条件下通过将磷酸肌酸掺入壳聚糖分子链中合成了磷酸化壳聚糖水凝胶。磷酸基团的引入改善了蛋白质吸附和钙沉积的性能，而不影响水凝胶的形态。我们的结果表明，磷酸化壳聚糖水凝胶不仅可以促进碱性磷酸酶活性和矿化，还可以上调成骨相关基因和蛋白质的表达。同时，应用c-Jun氨基末端激酶抑制剂SP600125和p38丝裂原活化蛋白激酶抑制剂SB203580可在基因和蛋白质水平上抑制成骨相关标志物的表达。据我们所知，首次报道含磷生物聚合物通过JNK和p38信号通路促进成骨细胞的成骨分化。
