Work

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

Year: 2025

Type: article

Abstract: BACKGROUND: Effective 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. METHODS: Retrospective 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. RESULTS: Bone 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). CONCLUSION: Echinococcal infection promotes pathological osteoclastogenesis and osteolysis through IL-1β/c-Fos/NFATc1 signaling activation.

Source: Journal of Orthopaedic Surgery and Research

DOI: 10.1186/s13018-025-06505-5

Authors: Yelinaer Ayiheng, Wuluhan Mahan, Zengru Xie

Institutions: Xinjiang Medical University, First Affiliated Hospital of Xinjiang Medical University

Language: English

Topic: Parasitic infections in humans and animals

Subfield: Pathology and Forensic Medicine

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,090