A novel CB2 agonist peptide with bone-promoting activity

Osteoporosis is a common bone degenerative disease that seriously affects the lives of people with osteoporosis. Cannabinoid receptor subtype 2(CB2) as a potential target of osteopathy, is expected to improve the quality of life of osteoporosis patients and provide a new avenue for osteoporosis treatment. This study aims to utilize the CB2 structure for high-throughput peptide screening and validation of its osteogenic activity. We have constructed a database of bioactive peptides and a virtual peptide library for tripeptide screening. Use the AutoDock and Glide Methods for Docking to screen peptides with strong CB2 binding. Subsequently, the secondary docking is carried out using AutoDock Vina. We selected the top 10 bioactive peptides for further study.Validating the agonistic activity of the screened peptides agoinst CB2 by measuring cAMP accumulation in HEK293 cells expressing CB2, we found that three peptides (APOCB2R3, APOCB2R4, APOCB2R7) significantly activated CB2. Then, we evaluated the regulatory effect of the screened compounds on bone metabolism in different osteoblasts and found that the peptides had osteogenic activity. In summary, combined with virtual screening and cell-based experiments, we successfully identified potential peptides with CB2 agonist and osteogenic activity, providing a new avenue for the development of osteoporosis drugs.