2022, Vol. 26 ›› Issue (29): 4643-4650

Bushen Jianpi Huoxue Recipe is closely related to the target of histone demethylase JMJD2B in promoting osteogenic differentiation in osteoporosis: an in vitro cell experimental verification

Luo Zhen1, Huang Yuxi1, Chai Shengting1, 2, Li Feilong1, 2, Chen Qunqun1, 2   

Abstract: BACKGROUND: Bushen Jianpi Huoxue Recipe is an empirical prescription commonly used in the treatment of osteoporosis. However, its potential molecular mechanism needs to be further explored.
OBJECTIVE: To explore the potential molecular mechanism of Bushen Jianpi Huoxue Recipe in the treatment of osteoporosis based on network pharmacology, and to verify the possibility of its effect through histone methylation modification.
METHODS: Based on the network pharmacology, the active drug components and action targets of Bushen Jianpi Huoxue Recipe were screened from relevant database using relevant software, and the targets of osteoporosis-related diseases were obtained. The intersected targets were obtained and identified as the potential targets of Bushen Jianpi Huoxue Recipe in the treatment of osteoporosis. The drug component-target network was constructed by String and Cytoscape software, and the core targets were screened out. The functions and genes related to histone modification were extracted based on the results of GO biological analysis, and the target genes related to histone modification were screened from the core targets. Literature analysis was performed to indicate the possible biological role of target genes in osteoporosis and histone modification. In vitro cell experiments were conducted to verify the effect of Bushen Jianpi Huoxue Recipe on osteogenic differentiation in the treatment of osteoporosis via the regulation of histone demethylase JMJD2B that is closely related to the target.
RESULTS AND CONCLUSION: A total of 118 active drug components related to osteoporosis were identified, with 165 corresponding targets. The core targets were IL6, TP53, FOS, JUN, STAT3, RELA, CCND1, MYC, MAPK1, MAPK8, MAPK14, VEGFA, AKT1, ESR1, TNF, NR3C1 and so on. GO biological function analysis showed that the biological functions such as drug response, nutrition level response, oxidative stress response, steroid hormone response, transcriptional regulation, transcription factor binding, phosphatase binding, protease binding, and steroid hormone receptor activity were closely related to the common targets. The core targets such as MAPK8, VEGFA and TP53 were related to histone modification; luteolin, quercetin, and kaempferol might be the main drug components affecting histone modification in the treatment of osteoporosis. Results from the in vitro cell experiment revealed that the expression of osteogenesis-related alkaline phosphatase, JMJD2B and RUNX2 protein increased significantly in rat bone marrow mesenchymal stem cells treated with Bushen Jianpi Huoxue Recipe. Histone demethylase JMJD2B, which is closely related to the pharmacological target of Bushen Jianpi Huoxue Recipe, might promote osteogenic differentiation in the treatment of osteoporosis.
Key words: histone demethylase, osteoporosis, JMJD2B, osteogenic differentiation, network pharmacology