Epigallocatechin gallate regulates inflammatory responses and new bone formation through Wnt/β-Catenin/COX-2 pathway in spondyloarthritis

Int Immunopharmacol. 2021 Sep:98:107869. doi: 10.1016/j.intimp.2021.107869. Epub 2021 Jun 18.

Abstract

Objective: Spondyloarthritis (SpA) is mainly characterized by bone erosion, new bone formation, inflammation and potential disability. Epigallocatechin gallate (EGCG) has been proved to be closely related with the regulation of inflammation and bone metabolism. However, whether EGCG could improve SpA remains unclear.

Methods: SpA animal model was established using proteoglycan. Cell proliferation were measured by CCK-8 assay. The mRNA expression levels of genes were detected using qRT-PCR, protein levels were assessed via western blotting and immunohistochemistry. ELISA assay was performed to examined the inflammatory cytokine release. Lesions in spine cartilage tissues were observed using hematoxylin-eosin (HE) and Safranin O staining. Alkaline phosphatase (ALP) assay and Alizarin Red S staining was used to investigate osteoblast mineralization.

Results: We found that EGCG could inhibit inflammation and new bone formation in SpA mice. Besides, inflammatory factor expression and osteogenic differentiation in osteoblasts isolated from SpA mice were also decreased by EGCG. Further, EGCG treatment suppressed the activation of Wnt/β-Catenin/COX-2 pathway and the activator of this pathway partially reversed the effects of EGCG on inflammation and osteoblast differentiation.

Conclusions: EGCG repressed inflammatory responses and new bone formation, and further improved SpA through Wnt/β-Catenin/COX-2 pathway. Our findings may provide a new thought for the prevention and treatment of SpA.

Keywords: EGCG; Inflammation; New bone formation; Spondyloarthritis; Wnt/β-Catenin/COX-2.

MeSH terms

  • Administration, Oral
  • Animals
  • Arthritis, Experimental / drug therapy*
  • Arthritis, Experimental / immunology
  • Catechin / analogs & derivatives*
  • Catechin / pharmacology
  • Catechin / therapeutic use
  • Cyclooxygenase 2 / metabolism
  • Drug Evaluation, Preclinical
  • Humans
  • Male
  • Mice
  • Osteogenesis / drug effects*
  • Osteogenesis / immunology
  • Spondylarthritis / drug therapy*
  • Spondylarthritis / immunology
  • Wnt Signaling Pathway / drug effects*
  • Wnt Signaling Pathway / immunology
  • beta Catenin / metabolism

Substances

  • CTNNB1 protein, mouse
  • beta Catenin
  • Catechin
  • epigallocatechin gallate
  • Ptgs2 protein, mouse
  • Cyclooxygenase 2