BackgroundOsteoporosis is a metabolic bone disease characterized by dysregulated osteoclast activity, resulting in increased bone degradation and compromised bone microarchitecture. While the interconnection between osteoclast differentiation and cellular energy metabolism has become increasingly recognized, the role of pyrimidine metabolism in this process remains largely undefined.MethodsIntegrative multi-omics analyses were performed to characterize transcriptional and metabolic alterations during receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclast differentiation.
The effects of uridine (UD) on osteoclast development and resorptive function were assessed in vitro using RAW264.7 cells and bone marrow-derived macrophages (BMMs). In vivo effects of UD on bone loss were evaluated in an ovariectomized (OVX) mouse model.ResultsIntegrative analyses revealed distinct metabolic remodeling during osteoclast differentiation and identified UD as a pivotal metabolite that showed a significant decline upon RANKL stimulation.
Experimental evidence indicated that exogenous UD supplementation significantly suppressed osteoclast development and resorptive function, along with a reduction in the expression of nuclear factor of activated T cells c1 (NFATc1) and cathepsin K (CTSK). In OVX mice, UD administration improved trabecular microarchitecture, reduced osteoclast burden, and mitigated bone loss.
Frontiers in Immunology published a clinical update in Infectious Disease on 27 Apr 2026.
The item focuses on Uridine inhibits ROS-mediated osteoclast differentiation and alleviates osteoporosis via modulation of PI3K/Akt–FoxO signaling.
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