Mediation of Cartilage Matrix Degeneration and Fibrillation by Decorin in Post-traumatic Osteoarthritis

Arthritis Rheumatol. 2020 Aug;72(8):1266-1277. doi: 10.1002/art.41254. Epub 2020 Jul 8.

Abstract

Objective: To elucidate the role of decorin, a small leucine-rich proteoglycan, in the degradation of cartilage matrix during the progression of post-traumatic osteoarthritis (OA).

Methods: Three-month-old decorin-null (Dcn-/- ) and inducible decorin-knockout (Dcni KO ) mice were subjected to surgical destabilization of the medial meniscus (DMM) to induce post-traumatic OA. The OA phenotype that resulted was evaluated by assessing joint morphology and sulfated glycosaminoglycan (sGAG) staining via histological analysis (n = 6 mice per group), surface collagen fibril nanostructure via scanning electron microscopy (n = 4 mice per group), tissue modulus via atomic force microscopy-nanoindentation (n = 5 or more mice per group) and subchondral bone structure via micro-computed tomography (n = 5 mice per group). Femoral head cartilage explants from wild-type and Dcn-/- mice were stimulated with the inflammatory cytokine interleukin-1β (IL-1β) in vitro (n = 6 mice per group). The resulting chondrocyte response to IL-1β and release of sGAGs were quantified.

Results: In both Dcn-/- and Dcni KO mice, the absence of decorin resulted in accelerated sGAG loss and formation of highly aligned collagen fibrils on the cartilage surface relative to the control (P < 0.05). Also, Dcn-/- mice developed more salient osteophytes, illustrating more severe OA. In cartilage explants treated with IL-1β, loss of decorin did not alter the expression of either anabolic or catabolic genes. However, a greater proportion of sGAGs was released to the media from Dcn-/- mouse explants, in both live and devitalized conditions (P < 0.05).

Conclusion: In post-traumatic OA, decorin delays the loss of fragmented aggrecan and fibrillation of cartilage surface, and thus, plays a protective role in ameliorating cartilage degeneration.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aggrecans / metabolism
  • Animals
  • Cartilage, Articular / metabolism*
  • Chondrocytes / metabolism
  • Collagen / metabolism
  • Decorin / metabolism*
  • Disease Models, Animal
  • Glycosaminoglycans / metabolism
  • Interleukin-1beta / metabolism
  • Matrilin Proteins / metabolism
  • Menisci, Tibial / metabolism
  • Mice
  • Mice, Knockout
  • Osteoarthritis / etiology
  • Osteoarthritis / metabolism*
  • Osteophyte / metabolism
  • Wounds and Injuries / complications

Substances

  • Aggrecans
  • Decorin
  • Glycosaminoglycans
  • IL1B protein, mouse
  • Interleukin-1beta
  • Matrilin Proteins
  • A73025
  • Collagen