Transgenic PDGF-BB sericin hydrogel potentiates bone regeneration of BMP9-stimulated mesenchymal stem cells through a crosstalk of the Smad-STAT pathways  

作　　者：Hui-Jie Zhang Fu-Shu Li Feng Wang Han Wang Tong-Chuan He Russell R.Reid Bai-Cheng He Qingyou Xia 

机构地区：[1]Key Laboratory of Biochemistry and Molecular Pharmacology of Chongqing,Chongqing Medical University,Chongqing 400016,China [2]Department of Pharmacology,School of Pharmacy,Chongqing Medical University,Chongqing 400016,China [3]Department of Pharmacy,Chongqing Emergency Medical Center,Chongqing University Central Hospital,Chongqing 400014,China [4]Biological Science Research Center,Chongqing Key Laboratory of Sericultural Science,Chongqing Engineering and Technology Research Center for Novel Silk Materials,Southwest University,Chongqing 400715,China [5]Department of Pharmacy,Panzhou People’s Hospital,Guizhou 553599,China [6]Molecular Oncology Laboratory,Department of Orthopaedic Surgery and Rehabilitation Medicine,The University of Chicago Medical Center,Chicago,IL 60637,USA [7]Laboratory of Craniofacial Biology and Development,Department of Surgery Section of Plastic Surgery,The University of Chicago Medical Center,Chicago,IL 60637,USA

出　　处：《Regenerative Biomaterials》2023年第1期181-193,共13页再生生物材料（英文版）

基　　金：supported by the National Natural Science Foundation of China(81702154);partly from the Chongqing Science and Technology Commission(cstc2020jcyj-cxttX0001);the State Key Laboratory of Silkworm Genome Biology(SKLSGB161718-4);the National Institutes of Health(NIH)Research Project Grant Program(DE030480).

摘　　要：Silk as a natural biomaterial is considered as a promising bone substitute in tissue regeneration.Sericin and fibroin are the main components of silk and display unique features for their programmable mechanical properties,biocompatibility,biodegradability and morphological plasticity.It has been reported that sericin recombinant growth factors(GFs)can support cell proliferation and induce stem cell differentiation through cross-talk of signaling pathways during tissue regeneration.The transgenic technology allows the productions of bioactive heterologous GFs as fusion proteins with sericin,which are then fabricated into solid matrix or hydrogel format.Herein,using an injectable hydrogel derived from transgenic platelet-derived GF(PDGF)-BB silk sericin,we demonstrated that the PDGF-BB sericin hydrogel effectively augmented osteogenesis induced by bone morphogenetic protein(BMP9)-stimulated mesenchymal stem cells(MSCs)in vivo and in vitro,while inhibiting adipogenic differentiation.Further gene expression and protein-protein interactions studies demonstrated that BMP9 and PDGF-BB synergistically induced osteogenic differentiation through the cross-talk between Smad and Stat3 pathways in MSCs.Thus,our results provide a novel strategy to encapsulate osteogenic factors and osteoblastic progenitors in transgenic sericin-based hydrogel for robust bone tissue engineering.

关 键 词：BIOMATERIALS growth factor BMP9 OSTEOGENESIS 

分 类 号：R318[医药卫生—生物医学工程] TQ427.26[医药卫生—基础医学]