Pathogenesis in a Rat Model of Osteosarcopenia Based on Network Pharmacology and Experimental Validation

doi:10.19803/j.1672-8629.20250762

Abstract

Abstract: Objective To explore the molecular mechanisms of osteosarcopenia (OS) based on network pharmacology and animal experiments. Methods Common targets of sarcopenia and osteoporosis were identified from multiple databases. A protein-protein interaction network was constructed to screen for hub genes, followed by GO and KEGG enrichment analyses. An OS rat model was established using a combined approach and randomly divided into a sham operation (Sham) group and an ovariectomy plus dexamethasone (OVX+DXM) group. Rats in the OVX+DXM group received daily intraperitoneal injections of dexamethasone (1 mg·kg^-1 for 2 weeks) while the Sham group was administered with an equal volume of normal saline. After model validation by HE staining, micro-CT, and ELISA, target protein expressions were determined by Western blot. Results The core hub genes in OS included INS, IL-6, and IL-1β. GO analysis suggested that OS was associated with such biological processes as muscle cell differentiation, inflammation, and apoptosis. KEGG analysis revealed the involvement of PI3K/AKT, NF-κB, and PPAR signaling pathways. Animal experiments showed that in the OVX+DXM group grip strength was significantly reduced (P<0.01), serum levels of irisin, calcium and alkaline phosphatase decreased (P<0.05), bone microstructure deteriorated on micro-CT, muscle fiber arrangement disorganized, and bone marrow cavities enlarged on HE staining. Western blot analysis demonstrated that the expressions of OPG, PGC-1α, Runx2, and PI3K were significantly downregulated while those of PPARγ, RANKL, and NF-κB were significantly upregulated in femoral tissue (P<0.05). Conclusion PI3K, NF-κB, and PPARγ can participate in the pathogenesis of OS, and the pathological process is likely associated with insufficient bone/muscle anabolism caused by reduced activity of the PI3K/AKT signal pathway, accelerated degradation of bone resorption/muscle proteins due to activation of the NF-κB signal pathway, and bone marrow/muscle adipogenesis induced by increased activation of the PPARγ signal pathway.

Key words: Network Pharmacology, Osteosarcopenia, Pathogenesis, Experimental Validation, Signaling Pathway

CLC Number:

R965.1

MA Ningning, ZHU Lin, XIAN Junying, FENG Xue, ZHANG Caijuan, WANG Dunfang, LIU Haifan, LIU Bin, LIU Jianyao, LI Yuehua, YANG Weipeng. Pathogenesis in a Rat Model of Osteosarcopenia Based on Network Pharmacology and Experimental Validation[J]. Chinese Journal of Pharmacovigilance, 2026, 23(2): 155-161.

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https://zgywjj.magtechjournal.com/EN/Y2026/V23/I2/155

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