ArticleJournal of orthopaedic surgery and research2025
Mechanistic role of the IL-1β/c-Fos/NFATc1 signaling axis in echinococcal infection-promoted osteoclast differentiation and activation in pathological osteolysis: a prospective controlled trial.
Article in Journal of orthopaedic surgery and research, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundEffective therapies remain elusive for devastating osteolysis in osseous echinococcosis, thus necessitating mechanistic exploration. To elucidate the molecular mechanism by which echinococcal infection promotes osteoclast differentiation and activation via the IL-1β/c-Fos/NFATc1 signaling axis in pathological osteolysis of osseous echinococcosis.
methodsRetrospective RT-qPCR analysis quantified mRNA expression of osteoclastogenesis-associated inflammatory factors (TNF-α, IL-1β, IL-6, IL-8) in bone cyst tissues from 21 osseous echinococcosis patients versus histologically normal bone adjacent to tumors in 21 matched bone tumor controls. Murine RAW 264.7 monocytes/macrophages were divided into: (i) Untreated control; (ii) Osteoclast induction (100 ng/mL RANKL + 25 ng/mL M-CSF); (iii-v) Induction + hydatid antigen B (25/50/75 ng/mL); (vi) Induction + antigen B (75 ng/mL) + IL-1β antagonist (canakinumab, 10 ng/mL). TRAP staining identified osteoclasts (≥ 3 nuclei), with positive cell percentage calculated across ≥ 5 random fields. ELISA measured cytokine levels in supernatants; Western blot quantified c-Fos, NFATc1, Cathepsin K, and MMP9 expression.
resultsBone cyst tissues exhibited elevated TNF-α, IL-1β, IL-6, and IL-8 mRNA versus controls (P < 0.05). Antigen B (25-75 ng/mL) dose-dependently increased TRAP⁺ cells and inflammatory cytokines versus induction group (P < 0.05). c-Fos, NFATc1, Cathepsin K, and MMP9 were upregulated in induction and antigen B (75 ng/mL) groups versus control (P < 0.05), with further elevation in antigen B (75 ng/mL) group versus induction (P < 0.05). Canakinumab reversed these protein increases versus antigen B (75 ng/mL) group (P < 0.05).
conclusionEchinococcal infection promotes pathological osteoclastogenesis and osteolysis through IL-1β/c-Fos/NFATc1 signaling activation.
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