Fasciola helminth defense molecule-1 protects against experimental arthritis by inhibiting osteoclast formation and function without modulating the systemic immune response

FASEB J. 2020 Jan;34(1):1091-1106. doi: 10.1096/fj.201901480RR. Epub 2019 Nov 28.


An inverse correlation between helminth infection and the autoimmune disease appears to be contributed by the anti-inflammatory factors produced by these organisms. Suppressing osteoclast function without affecting the systemic immunological response is an emerging therapeutic strategy for rheumatoid arthritis (RA). We observed that a synthetic peptide corresponding to 34 amino acids of C-terminal sequence of Fasciola helminth defense molecule-1 (C-FhHDM-1) inhibited RANKL-induced osteoclast formation and lysosomal acidification with an attendant upregulation of sequestome1/p62, a negative regulator of NF-κB expression. C-FhHDM-1 also suppressed RANKL production from osteoblasts. Macrophages are the major inflammatory cells in the joints of RA and C-FhHDM-1 suppressed ICAM-1 (an inflammatory surrogate) expression in these cells. In a murine model of collagen II-induced arthritis (CIA), C-FhHDM-1 improved clinical score, protected against cartilage destruction, and maintained bone mass and bone architecture of joints compared with the CIA group. C-FhHDM-1 suppressed the CIA-induced expression of TNF, IL-17, and IFN-γ in joints but not their serum levels. The peptide also had no effect on the CIA-induced suppression of T regulatory response. We conclude that C-FhHDM-1 has a joint-specific protective effect in experimental arthritis without mitigating systemic inflammation, and thus could become an adjuvant anti-arthritis therapy to prevent RA-induced osteopenia.

Keywords: bone; cartilage; collagen‐induced arthritis; helminth defense molecule; lysosome; osteoclast.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Arthritis, Experimental / drug therapy
  • Arthritis, Experimental / metabolism*
  • Cell Differentiation
  • Fasciola / genetics
  • Fascioliasis / immunology
  • Helminth Proteins / genetics
  • Immunity
  • Intercellular Adhesion Molecule-1 / metabolism
  • Macrophages / metabolism
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred DBA
  • Osteoblasts / drug effects
  • Osteoblasts / metabolism
  • Osteoclasts / drug effects*
  • Osteoclasts / metabolism
  • Peptides / chemistry
  • Peptides / pharmacology*
  • RANK Ligand / metabolism


  • Helminth Proteins
  • Icam1 protein, mouse
  • Peptides
  • RANK Ligand
  • Intercellular Adhesion Molecule-1