Agents that block fibronectin fragment-mediated cartilage damage also promote repair.

Abstract

The objective was to determine if agents that suppress catabolism might also enhance repair of irreversibly damaged cartilage. Articular cartilage from bovine metacarpophalangeal joints was studied in explant culture. Fibronectin fragments or IL-1 alpha, which potently cause proteoglycan (PG) loss from cartilage, were added to cultures also containing the catabolism-blocking agents: insulin-like growth factor-1, or N-acetylcysteine, or Arg-Gly-Asp-Ser peptide, and the effects of these agents on blocking PG loss determined. To test for repair or restoration of PG, cartilage was first damaged, damage agents removed and inhibitory agents added. Each mean and SD value for cartilage PG content was determined by assays of papain digests of cartilage from three similar cultures. The agents either partially or fully blocked PG loss and promoted repair. Normally irreversible cartilage damage was reversed by slowing ongoing catabolic processes during attempted repair. Thus, catabolic inhibitors have reparative potential.