The articular cartilage preservative effects of genistein in an experimental model of knees osteoarthritis

Appl Physiol Nutr Metab. 2021 Nov;46(11):1331-1336. doi: 10.1139/apnm-2020-0958. Epub 2021 May 14.

Abstract

The study aimed to investigate the preservative effects of genistein on articular cartilage in an experimental model of knee osteoarthritis in rats. Thirty male Wistar rats were assigned to 3 equal groups: sham group, osteoarthritis control group (OAG), and genistein-treated osteoarthritis group (GTG). Intra-articular injections of monosodium iodoacetate were used for osteoarthritis induction. After 2 weeks of rest for the induction of the inflammatory process, genistein (30 mg/kg/day) vs. saline gavage was administered for 8 weeks. The expression of matrix metalloproteinase (MMP)-8 and MMP-13, Sox5/Sox6, Indian hedgehog (IHH), and Col2 were evaluated in medial femoral condyle sections by immunohistochemical staining. The number of chondrocytes and cartilage thicknesses were also measured and compared among the groups. No significant change in cartilage thickness was observed in GTG compared with OAG (p = 0.188). Chondrocyte count was significantly higher in the articular cartilage of GTG compared with OAG (p = 0.006). Induction of osteoarthritis significantly increased the expression of MMP-8, MMP-13, and IHH, but decreased Col2, Sox5, and Sox6 expression (p < 0.001); these were partially prevented in the GTG. Our findings support the effectiveness of genistein treatment in the prevention of articular cartilage damage in the experimental model of knee osteoarthritis. The proposed mechanism of action is through the suppression of the MMP, IHH, and Col2 pathways, besides the induction of Sox5 and Sox6 expression. Novelty: Genistein prevents articular cartilage damage in the experimental model of knee osteoarthritis. The osteoprotective effect is manifested by the modulation of expression of MMP, Sox, IHH, and Col2 proteins.

Keywords: Indian hedgehog; Sox; arthrose; genistein; génistéine; matrix metalloproteinases; métalloprotéinases matricielles; osteoarthritis.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology*
  • Anti-Inflammatory Agents / therapeutic use
  • Cartilage, Articular / cytology
  • Cartilage, Articular / drug effects*
  • Cell Count
  • Collagen Type II / genetics
  • Collagen Type II / metabolism
  • Disease Models, Animal
  • Gene Expression
  • Genistein / pharmacology*
  • Genistein / therapeutic use
  • Hedgehog Proteins / genetics
  • Hedgehog Proteins / metabolism
  • Immunohistochemistry
  • Knee Joint*
  • Male
  • Matrix Metalloproteinase 13 / genetics
  • Matrix Metalloproteinase 13 / metabolism
  • Matrix Metalloproteinase 8 / genetics
  • Matrix Metalloproteinase 8 / metabolism
  • Osteoarthritis, Knee / metabolism
  • Osteoarthritis, Knee / prevention & control*
  • Phytoestrogens / pharmacology*
  • Phytoestrogens / therapeutic use
  • Rats
  • Rats, Wistar
  • SOXD Transcription Factors / genetics
  • SOXD Transcription Factors / metabolism

Substances

  • Anti-Inflammatory Agents
  • Collagen Type II
  • Hedgehog Proteins
  • Phytoestrogens
  • SOXD Transcription Factors
  • Genistein
  • Matrix Metalloproteinase 13
  • Matrix Metalloproteinase 8