Alloferon-1 ameliorates estrogen deficiency-induced osteoporosis through dampening the NLRP3/caspase-1/IL-1β/IL-18 signaling pathway

Int Immunopharmacol. 2023 Nov;124(Pt B):110954. doi: 10.1016/j.intimp.2023.110954. Epub 2023 Sep 22.

Abstract

Alloferon-1 is an insect polypeptide that has anti-inflammatory, antitumor and antiviral activity. This study aimed to determine the effects of alloferon-1 on estrogen deficiency-induced osteoporosis and explore the associated mechanism using a murine model of ovariectomy (OVX)-induced osteoporosis. Results showed that alloferon-1 prevented ovariectomy‑induced body weight gain, bone loss and bone mineral content reduction, affected biochemical markers of bone turnover, and restored the microstructure of bone trabeculae. Moreover, alloferon-1 suppressed the expression of the ovariectomy‑mediated inflammatory cytokines in the vertebrae bone tissues, including nucleotide-binding oligomerization domain-like-receptor family pyrin domain-containing 3 (NLRP3), cysteinyl aspartate specific proteinase-1 (Caspase-1), interleukin 1β (IL-1β) and interleukin 18 (IL-18) which were determined by immunofluorescence staining and western blot. Overall, the present study provides evidence for the effectiveness of alloferon-1 against estrogen deficiency-induced osteoporosis, suggesting an alternative drug or an auxiliary modulator for the treatment of postmenopausal osteoporosis (PMOP).

Keywords: Alloferon-1; IL-18; IL-1β; NLRP3; Postmenopausal osteoporosis.

MeSH terms

  • Animals
  • Caspase 1 / metabolism
  • Estrogens / therapeutic use
  • Female
  • Humans
  • Inflammasomes / metabolism
  • Interleukin-18
  • Interleukin-1beta / metabolism
  • Mice
  • NLR Family, Pyrin Domain-Containing 3 Protein* / metabolism
  • Osteoporosis* / drug therapy
  • Peptides
  • Signal Transduction

Substances

  • NLR Family, Pyrin Domain-Containing 3 Protein
  • Inflammasomes
  • Alloferon
  • Interleukin-18
  • Caspase 1
  • Interleukin-1beta
  • Peptides
  • Estrogens