Mono-iodoacetate-induced experimental osteoarthritis: a dose-response study of loss of mobility, morphology, and biochemistry

Arthritis Rheum. 1997 Sep;40(9):1670-9. doi: 10.1002/art.1780400917.


Objective: To characterize the dose-responsiveness of morphologic and biochemical chondral changes relative to mobility in mono-iodoacetate (MIA)-induced osteoarthritis (OA) in rats.

Methods: Rat mobility was assessed by biotelemetry. Articular lesions were characterized by macroscopic and histologic examinations. Cartilage proteoglycan metabolism was evaluated by the 1,9-dimethylmethylene blue dye binding assay and by radiosulfate incorporation in patellar cartilage.

Results: Spontaneous locomotor activity was rapidly, transiently, and dose-dependently decreased after MIA injection into rat knees (primary response). Thereafter, only high doses (0.3 mg and 3.0 mg) led to a secondary progressive long-term loss of spontaneous mobility on day 15, when subchondral bone was exposed. These 2 doses resulted in significant changes in cartilage proteoglycan concentration at day 15 and a strong inhibition of anabolism in the peripheral patellae by day 2, contrasting with the effects of lower doses (0.01, 0.03, and 0.1 mg).

Conclusion: When a sufficient dose of MIA is used, this model can easily and quickly reproduce OA-like lesions and functional impairment in rats, similar to that observed in human disease. These parameters, as well as proteoglycan metabolism, could serve as indicators for studying chondroprotective drugs, or for evaluating the ability of imaging techniques to detect and evaluate chondral lesions.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cartilage, Articular / drug effects
  • Cartilage, Articular / metabolism
  • Cartilage, Articular / pathology
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Enzyme Inhibitors / toxicity*
  • Glycosaminoglycans / biosynthesis
  • Injections, Intra-Articular
  • Iodoacetates / toxicity*
  • Knee Joint / drug effects
  • Knee Joint / pathology
  • Male
  • Motor Activity / drug effects*
  • Motor Activity / physiology
  • Osteoarthritis / chemically induced*
  • Osteoarthritis / pathology
  • Osteoarthritis / physiopathology
  • Patella / chemistry
  • Proteoglycans / biosynthesis
  • Rats
  • Rats, Wistar


  • Enzyme Inhibitors
  • Glycosaminoglycans
  • Iodoacetates
  • Proteoglycans