Regulating the bioactivity of non-glycosylated recombinant human bone morphogenetic protein-2 to enhance bone regeneration

Yuanman Yu; Rui Chen; Xinye Chen; Jing Wang; Changsheng Liu

doi:10.1016/j.bioactmat.2024.04.018

Regulating the bioactivity of non-glycosylated recombinant human bone morphogenetic protein-2 to enhance bone regeneration

Bioact Mater. 2024 Apr 30:38:169-180. doi: 10.1016/j.bioactmat.2024.04.018. eCollection 2024 Aug.

Authors

Yuanman Yu^{1

2

3}, Rui Chen^{1

2}, Xinye Chen^{1

3}, Jing Wang^{1

2

3}, Changsheng Liu^{2

3}

Affiliations

¹ The State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai, 200237, PR China.
² Key Laboratory for Ultrafine Materials of Ministry of Education, Engineering Research Center for Biomedical Materials of Ministry of Education, School of Materials Science and Engineering, East China University of Science and Technology, Shanghai, 200237, PR China.
³ Frontiers Science Center for Materiobiology and Dynamic Chemistry, East China University of Science and Technology, Shanghai, 200237, PR China.

Abstract

Recombinant human bone morphogenetic protein-2 (rhBMP-2) is the predominant growth factor that effectively induces osteogenic differentiation in orthopedic procedures. However, the bioactivity and stability of rhBMP-2 are intrinsically associated with its sequence, structure, and storage conditions. In this study, we successfully determined the amino acid sequence and protein secondary structure model of non-glycosylated rhBMP-2 expressed by an E. coli expression system through X-ray crystal structure analysis. Furthermore, we observed that acidic storage conditions enhanced the proliferative and osteoinductive activity of rhBMP-2. Although the osteogenic activity of non-glycosylated rhBMP-2 is relatively weaker compared to glycosylated rhBMP-2; however, this discrepancy can be mitigated by incorporating exogenous chaperone molecules. Overall, such information is crucial for rationalizing the design of stabilization methods and enhancing the bioactivity of rhBMP-2, which may also be applicable to other growth factors.

Keywords: Osteogenic activity; Protein stability; Recombinant human bone morphogenetic protein-2; Sulfated polysaccharide.