Integrative network toxicology, molecular docking, and in vitro experiments identify SLC6A2 as a novel candidate target in nicotine-induced osteoporosis.

Authors

Bo Lu, Xuwang Gao, Qian Wang, Yangyang Li, Shuang Chai, Mingyu Zhao

Published in

Experimental gerontology. Pages 113316. Sep 10, 2026. Epub Sep 10, 2026.

Abstract

In recent years, the health problems attributable to cigarette smoke (CS) have attracted widespread attention. However, the pathogenic mechanisms underlying osteoporosis development induced by nicotine, a neuroactive component of CS, remain unclear. In this study, we examined a potential molecular mechanism underlying nicotine-induced osteoporosis by network toxicology, molecular docking, molecular dynamics (MD) simulation, and in vitro experiments. On screening multiple databases, we identified 47 overlapping targets for nicotine- and osteoporosis-related genes, and subsequently performed protein-protein interaction (PPI) analysis on the identified targets. KEGG analysis suggested that the potential targets were mainly involved in the calcium, PI3K-Akt, and MAPK pathways. We identified seven core targets using five algorithms, among which SLC6A2 exhibited the strongest predicted binding affinity. Molecular docking confirmed good binding affinities between nicotine and these core targets, and molecular dynamics simulation verified the stability of the nicotine-SLC6A2 complex. Moreover, in vitro experiments further confirmed that nicotine significantly inhibits osteogenic differentiation of MC3T3-E1 cells, and differentially regulates the transcriptional expression of all seven core targets, with SLC6A2 being one of the downregulated ones. This identifies a previously unrecognized neural-related target (SLC6A2) in nicotine-induced bone toxicity. Our study provides a theoretical basis for developing multi-target regulation strategy that could contribute to mitigating the bone toxicity of complex environmental toxins.

PMID:
42722212
Bibliographic data and abstract were imported from PubMed on 11 Sep 2026.

Read full publication at:
Please sign in to see all details.

Stats

1-terrible, 9-excellent. How would you rate this publication? Sign in in to submit your rating.

Post a comment

You need to be signed in to post comments. You can sign in here.

Comments

There are no comments yet.