4.7 Article

Study on the mechanism and pharmacokinetics of HB-NC4 based on C5b-9 target in the treatment of osteoarthritis

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DOI: 10.1016/j.bbadis.2023.166699

Keywords

Osteoarthritis; C5b-9; Fusion protein; Complement system

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In this study, a fusion protein was introduced and its mechanism to alleviate osteoarthritis (OA) was discussed. The targeted protein HB-NC4 showed better binding ability to chondrocytes and had a prolonged half-life period. HB-NC4 affected the levels of C3 and C5 and inhibited the formation of the membrane-attack complex, thereby affecting the expression of MAPK signalling pathway-related proteins to treat OA. This study provides a new method for OA therapy based on fusion proteins.
Osteoarthritis (OA) is a chronic degenerative disease that mostly occurs in elderly individuals over 60 years old. The detailed pathogenesis of OA is unclear. Medicines available on the market are nonsteroidal antiinflammatory drugs. Therefore, in this study, a fusion protein was introduced, and the detailed mechanism that could alleviate OA was discussed. As a targeted protein, HB-NC4 showed better binding ability to chondrocytes, and its half-life period was prolonged compared to NC4 alone. In addition, HB-NC4 can not only affect the levels of C3 and C5, but also inhibit the formation of the membrane-attack complex (MAC, C5b-9), thereby further affecting the expression of MAPK signalling pathway-related proteins to achieve the goal of treating OA. Thus, in this study, we demonstrate the pharmacokinetics of HB-NC4 and its mechanism to alleviate OA by regulating the complement system and MAPK signalling pathway. This study provides a new method for OA therapy based on fusion proteins.

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