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bioRxiv · 10.1101/2025.09.26.678724

Deoxycholic acid (DCA) alleviates LPS-induced Inflammatory Bone Loss via modulating the Gut-Bone homeostasis

Yadav, S.·Rajput, S.·Saini, C.·Sharma, M.·Mishra, P. K.·Srivastava, R. K.
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Abstract

Osteoporosis and other forms of inflammatory bone loss are marked by disrupted bone remodelling resulting from an imbalance between osteoclast-mediated bone resorption and osteoblast-driven bone formation. This imbalance is often exacerbated by chronic inflammation and gut microbiota dysbiosis. Recently, attention has turned to gut-associated metabolites (GAMs) such as secondary bile acids, particularly deoxycholic acid (DCA), which act as immunomodulators influencing both systemic inflammation and bone metabolism. In this study, we investigated the role of DCA in inflammatory bone loss using an in vivo model, with a focus on osteoblast and osteoclast function, gut barrier integrity, and gut-microbiota diversity. DCA administration significantly suppressed osteoclastogenesis along with enhancing osteoblastogenesis, indicating its dual regulatory role in bone remodelling. Furthermore, DCA treatment enhanced gut integrity, reversed dysbiosis and reduced systemic inflammation by downregulating osteoclastogenic cytokines (TNF-, IL-6, IL-17, RANKL, etc.). These findings suggest that DCA mitigates LPS-induced inflammatory bone loss through a multifaceted mechanism involving direct effects on bone cells and restoration of gut integrity and homeostasis. Our results highlight the therapeutic potential of targeting the gut microbiota-derived bile acid pathway, particularly DCA, as a novel strategy for managing osteoporosis and other inflammatory bone disorders. O_FIG O_LINKSMALLFIG WIDTH=131 HEIGHT=200 SRC="FIGDIR/small/678724v1_ufig1.gif" ALT="Figure 1"> View larger version (46K): org.highwire.dtl.DTLVardef@1702fddorg.highwire.dtl.DTLVardef@568b38org.highwire.dtl.DTLVardef@1ce463aorg.highwire.dtl.DTLVardef@164a04d_HPS_FORMAT_FIGEXP M_FIG O_FLOATNOFigure 9.C_FLOATNO Graphical Abstract. Secondary bile acids act via FXR and TGR5 receptors on osteoclast and osteoblast cells and thereby regulate bone remodelling. C_FIG

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Yadav, S., Rajput, S., Saini, C., Sharma, M., Mishra, P. K., Srivastava, R. K.. 2025-09-29. Deoxycholic acid (DCA) alleviates LPS-induced Inflammatory Bone Loss via modulating the Gut-Bone homeostasis. https://doi.org/10.1101/2025.09.26.678724

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