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已发表论文
帕罗西汀作为炎性骨溶解治疗药物：机制见解与疗效
Authors Huang J , Wang Z, Liu J, Zhang J, Deng K, Huang S, Zhou S
Received 22 September 2025
Accepted for publication 15 January 2026
Published 27 January 2026 Volume 2026:20 561725
DOI https://doi.org/10.2147/DDDT.S561725
Checked for plagiarism Yes
Review by Single anonymous peer review
Peer reviewer comments 2
Editor who approved publication: Professor Anastasios Lymperopoulos
Junming Huang,1– 4,* Zhipeng Wang,1– 3,* Jun Liu,1– 3,* Jihong Zhang,1– 3 Kui Deng,1– 3 Shanhu Huang,1– 3 Song Zhou1– 3
1The Orthopedic Hospital, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, 330006, People’s Republic of China; 2Department of Sports Medicine, Orthopedic Hospital, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, 330006, People’s Republic of China; 3The Key Laboratory of Spine and Spinal Cord Diseases of Jiangxi Province, Nanchang, Jiangxi, 330006, People’s Republic of China; 4Postdoctoral Research Station, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, 330006, People’s Republic of China
*These authors contributed equally to this work
Correspondence: Shanhu Huang, Email hsh869@163.com Song Zhou, Email zhousong_tjmu@163.com
Background and Objective: Inflammatory osteolysis is a common feature of numerous orthopedic conditions, primarily driven by excessive osteoclast formation and activation. Recent studies have demonstrated that paroxetine, a selective serotonin reuptake inhibitor commonly prescribed for mental disorders, has significant anti-inflammatory effects. However, its effects on inflammatory osteolysis have not been fully elucidated. In this study, we investigated the effects and underlying mechanisms of paroxetine on osteoclast differentiation and function as well as its influence on inflammatory osteolysis in a murine model.
Methods: A mouse model of LPS-induced osteolysis was developed to assess the therapeutic efficacy of paroxetine in vivo. Utilizing the molecular structure of paroxetine, network pharmacology was used to predict principal targets and underlying mechanisms. The effect of paroxetine on osteoclast biology was subsequently investigated using morphological analysis, quantitative PCR (qPCR), and Western blotting.
Results: The findings from animal experiments demonstrated that paroxetine effectively mitigated LPS-induced bone loss by inhibiting osteoclast differentiation. In vitro analyses revealed that paroxetine suppresses osteoclast formation and bone resorption in a dose-dependent manner. Mechanistically, paroxetine downregulated osteoclast-specific genes and proteins while concurrently inhibiting the NF-κB and PI3K-AKT signaling pathways. Additionally, network pharmacology analysis identified PIK3CA as a pivotal target, substantiated by molecular docking studies (binding energy of − 8.0 kcal/mol) and rescue experiments employing PI3K (740 Y-P) and AKT (SC79) agonists, which reversed paroxetine-mediated inhibition of osteoclast formation.
Conclusion: Paroxetine attenuated LPS-induced inflammatory osteolysis in mice and suppressed osteoclast differentiation and function in vitro, an effect associated with down-regulation of NF-κB and PI3K-AKT signaling. These data indicate that paroxetine may represent a potential therapeutic candidate for osteolytic bone diseases. However, further validation is required to confirm its efficacy and safety in more complex pre-clinical models and in humans.
Keywords: paroxetine, osteolysis, osteoclast, PIK3CA
1The Orthopedic Hospital, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, 330006, People’s Republic of China; 2Department of Sports Medicine, Orthopedic Hospital, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, 330006, People’s Republic of China; 3The Key Laboratory of Spine and Spinal Cord Diseases of Jiangxi Province, Nanchang, Jiangxi, 330006, People’s Republic of China; 4Postdoctoral Research Station, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, 330006, People’s Republic of China
*These authors contributed equally to this work
Correspondence: Shanhu Huang, Email hsh869@163.com Song Zhou, Email zhousong_tjmu@163.com
Background and Objective: Inflammatory osteolysis is a common feature of numerous orthopedic conditions, primarily driven by excessive osteoclast formation and activation. Recent studies have demonstrated that paroxetine, a selective serotonin reuptake inhibitor commonly prescribed for mental disorders, has significant anti-inflammatory effects. However, its effects on inflammatory osteolysis have not been fully elucidated. In this study, we investigated the effects and underlying mechanisms of paroxetine on osteoclast differentiation and function as well as its influence on inflammatory osteolysis in a murine model.
Methods: A mouse model of LPS-induced osteolysis was developed to assess the therapeutic efficacy of paroxetine in vivo. Utilizing the molecular structure of paroxetine, network pharmacology was used to predict principal targets and underlying mechanisms. The effect of paroxetine on osteoclast biology was subsequently investigated using morphological analysis, quantitative PCR (qPCR), and Western blotting.
Results: The findings from animal experiments demonstrated that paroxetine effectively mitigated LPS-induced bone loss by inhibiting osteoclast differentiation. In vitro analyses revealed that paroxetine suppresses osteoclast formation and bone resorption in a dose-dependent manner. Mechanistically, paroxetine downregulated osteoclast-specific genes and proteins while concurrently inhibiting the NF-κB and PI3K-AKT signaling pathways. Additionally, network pharmacology analysis identified PIK3CA as a pivotal target, substantiated by molecular docking studies (binding energy of − 8.0 kcal/mol) and rescue experiments employing PI3K (740 Y-P) and AKT (SC79) agonists, which reversed paroxetine-mediated inhibition of osteoclast formation.
Conclusion: Paroxetine attenuated LPS-induced inflammatory osteolysis in mice and suppressed osteoclast differentiation and function in vitro, an effect associated with down-regulation of NF-κB and PI3K-AKT signaling. These data indicate that paroxetine may represent a potential therapeutic candidate for osteolytic bone diseases. However, further validation is required to confirm its efficacy and safety in more complex pre-clinical models and in humans.
Keywords: paroxetine, osteolysis, osteoclast, PIK3CA