Fib3-3 as a Biomarker for Osteoarthritis in a Rat Model with Metabolic Dysregulation

Cartilage. 2019 Jul;10(3):329-334. doi: 10.1177/1947603518754629. Epub 2018 Jan 24.

Abstract

Objective: Fibulin-3 is a glycoprotein highly expressed in osteoarthritic cartilage and inhibits angiogenesis and chondrocyte differentiation. Recent studies have indicated that fibulin-3 has potential value as a biomarker in osteoarthritis. The aim of the present study is to examine the role of 3 fibulin-3 peptides (Fib3-1, Fib3-2, and Fib3-3) and a type II collagen degradation product in a rat osteoarthritis model with systemic metabolic alterations combined with local cartilage damage.

Design: Forty, 12-week-old male, Wistar rats were randomly divided over 2 groups: a standard or a high-fat diet inducing metabolic dysregulation. After 12 weeks, articular cartilage damage was induced on the femoral condyles (groove model), in 1 knee joint in 14 rats of each diet group. At endpoint, blood was collected and serum was isolated. Enzyme-linked immunosorbent assay on all selected fibulin-3 fragments was performed from serum samples in addition to immunohistochemical analysis for Fib3-3.

Results: Serum concentrations of Fib3-3 were increased by 29.9%, when cartilage damage was induced in addition to a high-fat diet. Fib3-3 was also associated with an increased histological total joint degeneration (r = 0.435) and cartilage degeneration (r = 0.435). Immunostainings demonstrated increased Fib3-3 in the superficial cartilage of animals with high-fat diet and/or cartilage damage.

Conclusions: In the rat groove model combined with high-fat diet-induced metabolic dysregulation an increased Fib3-3 concentration was observed systemically, which is associated with local joint degeneration. This suggests that systemic Fib3-3 concentrations can indicate the status of joint degeneration and function as a biomarker in osteoarthritis.

Keywords: animal model; articular cartilage; osteoarthritis; biomarker.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biomarkers / blood
  • Cartilage, Articular / metabolism*
  • Cartilage, Articular / pathology
  • Collagen Type II / metabolism
  • Diet, High-Fat / adverse effects*
  • Extracellular Matrix Proteins / blood
  • Extracellular Matrix Proteins / metabolism*
  • Knee Joint / metabolism*
  • Knee Joint / pathology
  • Male
  • Metabolic Diseases / complications
  • Metabolic Diseases / metabolism
  • Metabolic Diseases / veterinary
  • Models, Animal
  • Osteoarthritis, Knee / blood*
  • Osteoarthritis, Knee / veterinary
  • Rats
  • Rats, Wistar

Substances

  • Biomarkers
  • Collagen Type II
  • EFEMP1 protein, human
  • Extracellular Matrix Proteins