Bushen Jiangu decoction alleviates osteoporosis by inhibiting MMP2 expression and activation of the MAPK pathway in vitro

Abstract

Objectives: To explore the precise mechanism of BJD against osteoporosis.

Methods: The active compounds and drug targets of BJD were screened from public databases and identified by HPLC. Differentially expressed genes related to osteoporosis were obtained, followed by overlapping targets of BJD and osteoporosis identified by PPI networks. Then the binding interactions between active compounds and hub targets were validated by molecular docking vina followed by molecular dynamics simulations. The effects and mechanisms of BJD against osteoporosis was validated through in vitro experiments.

Results: Three core active compounds in BJD were obtained. Molecular docking highlighted the affinity of the three compounds towards PTGS2, MMP2, and ADORA2B. In the LPS-induced MC3T3-E1 osteoblast cells, BJD significantly promoted cell viability and revived ALP activity. BJD reduced the expression of MMP2 and PTGS2 whereas elevated ADORA2B expression in the LPS-induced osteoblasts. BJD could alleviate osteoporosis by alleviating the activation of the MAPK signaling. Elevated levels of MMP2 impaired the migration capacity, and significantly increased ALP, COLI, OCN and OPN expression levels in LPS-induced MC3T3-E1 cells after BJD treatment, as well as the osteoblast calcium nodules were incompletely formed and deposited.

Conclusion: BJD alleviated osteoporosis by inhibiting MMP2 expression and activation of MAPK signaling.

Keywords: Bushen Jiangu decoction; Core active compounds; MAPK signaling pathway; Network pharmacology; Osteoporosis.