Synergistic effect between 2-N,6-O-sulfonated chitosan and bone morphogenetic protein-2

Ao Zheng; Xiao Wang; Jie Wang; Xianzhen Xin; Yuanman Yu; Yang Liu; Jing Wang; Kaige Lv; Lingyan Cao

doi:10.1016/j.carbpol.2021.117888

Synergistic effect between 2-N,6-O-sulfonated chitosan and bone morphogenetic protein-2

Carbohydr Polym. 2021 Jul 1:263:117888. doi: 10.1016/j.carbpol.2021.117888. Epub 2021 Mar 3.

Authors

Ao Zheng¹, Xiao Wang¹, Jie Wang¹, Xianzhen Xin¹, Yuanman Yu², Yang Liu², Jing Wang³, Kaige Lv⁴, Lingyan Cao⁵

Affiliations

¹ Department of Prosthodontics, Shanghai Engineering Research Center of Advanced Dental Technology and Materials, Shanghai Key Laboratory of Stomatology & Shanghai Research Institute of Stomatology, National Clinical Research Center for Oral Diseases, Shanghai Ninth People's Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, People's Republic of China.
² The State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai, People's Republic of China.
³ The State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai, People's Republic of China. Electronic address: biomatwj@163.com.
⁴ Department of Prosthodontics, Shanghai Engineering Research Center of Advanced Dental Technology and Materials, Shanghai Key Laboratory of Stomatology & Shanghai Research Institute of Stomatology, National Clinical Research Center for Oral Diseases, Shanghai Ninth People's Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, People's Republic of China. Electronic address: lvkaige@126.com.
⁵ Department of Prosthodontics, Shanghai Engineering Research Center of Advanced Dental Technology and Materials, Shanghai Key Laboratory of Stomatology & Shanghai Research Institute of Stomatology, National Clinical Research Center for Oral Diseases, Shanghai Ninth People's Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, People's Republic of China. Electronic address: cly_linya@163.com.

PMID: 33858564
DOI: 10.1016/j.carbpol.2021.117888

Abstract

The molecular structure of sulfonated chitosan is similar to heparin, and it has been proved to have some heparin functions. Studies have shown that heparin and bone morphogenetic protein-2 (BMP-2) have synergistic effects, but heparin has limitations in clinical application. In this paper, the synergistic effect of 2-N,6-O-sulfonated chitosan (26SCS) and BMP-2 was studied. The preparation of 26SCS was explored and 26SCS was co-cultured with bone marrow mesenchymal stem cells (BMSCs) to study the effects of 26SCS on the proliferation, adhesion behavior and osteogenic differentiation of BMSCs. The synergistic mechanism of 26SCS and BMP-2 was explored by circular dichroism and isothermal calorimetric titration. The results showed that 26SCS affected the secondary structure of BMP-2 protein, mainly caused the significant change of antiparallel conformation in β-fold, and then improved the biological activity of BMP-2 and showed a dose-dependent manner. 26SCS was expected to be a synergistic factor of BMP-2.

Keywords: 2-N,6-O-sulfonated chitosan; Bone morphogenetic protein-2; Chitosan; Synergistic effect.

MeSH terms

Alkaline Phosphatase / metabolism
Animals
Bone Morphogenetic Protein 2 / chemistry*
Bone Morphogenetic Protein 2 / metabolism*
Calcification, Physiologic / drug effects
Cell Adhesion / drug effects
Cell Differentiation / drug effects
Cell Proliferation / drug effects
Cells, Cultured
Chitosan / chemistry*
Chitosan / pharmacology*
Heparin / chemistry
Heparin / pharmacology
Mesenchymal Stem Cells / drug effects
Osteogenesis / drug effects
Protein Structure, Secondary / drug effects
Rabbits
Sulfur / chemistry

Substances

Bone Morphogenetic Protein 2
Sulfur
Heparin
Chitosan
Alkaline Phosphatase