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Updated: Jul 25, 2026
The Monoiodoacetate Model of Osteoarthritis Pain in the Mouse
Published on: May 16, 2016
Moderation of iodoacetate-induced experimental osteoarthritis in rats by matrix metalloproteinase inhibitors
M J Janusz1, E B Hookfin, S A Heitmeyer
1Procter & Gamble Pharmaceuticals, Inc., 8700 Mason-Montgomery Rd, Mason, Ohio 45040-9462, USA. janusz.mj@pg.com
Objective:
To determine the effect of matrix metalloproteinase (MMP) inhibitors in mono-iodoacetate-induced arthritis in rats.
Design:
The ability of compounds to inhibit MMPs in vitro was assessed kinetically using a quenched fluorescent substrate. Rats were injected with iodoacetate intraarticularly in one knee joint and damage to the tibial plateau was evaluated from digitized images captured using an image analyser and by histology. Collagenase and gelatinase activity in cartilage from iodoacetate injected knees were evaluated using(3)H-rat type I collagen and gelatin zymography, respectively.
Results:
Collagenase and gelatinase activity significantly increased in the knee cartilage of rats injected with iodoacetate with peak activity by day 7. Three MMP inhibitors were examined for their efficacy in the rat iodoacetate-induced arthritis model. Significant (P< 0.05) inhibition of cartilage damage was observed in animals treated orally with 35 mg/kg b.i.d. of the three different MMP inhibitors. Inhibition of cartilage damage by the MMP inhibitors ranged from 36-42%.
Conclusion:
MMP inhibitors are partially protective against cartilage and subchondral bone damage induced by iodoacetate. These results support an important role for MMPs in mediating the joint damage in this model of arthritis.
Insights
Matrix metalloproteinase (MMP) inhibitors partially protected against cartilage and bone damage in a rat arthritis model. These findings highlight the role of MMPs in mediating joint damage in arthritis.
Area of Science:
- Biochemistry
- Pharmacology
- Rheumatology
Background:
- Matrix metalloproteinases (MMPs) play a role in cartilage degradation.
- Mono-iodoacetate injection in rats is a model for osteoarthritis.
Purpose of the Study:
- To investigate the efficacy of MMP inhibitors in a rat model of mono-iodoacetate-induced arthritis.
- To assess the role of MMPs in joint damage.
Main Methods:
- MMP inhibition was assessed in vitro using kinetic assays.
- Arthritis was induced in rats via intra-articular iodoacetate injection.
- Cartilage damage was evaluated using imaging, histology, and enzymatic assays for collagenase and gelatinase activity.
Main Results:
- Collagenase and gelatinase activity increased significantly in rat knee cartilage post-iodoacetate injection.
- Three MMP inhibitors demonstrated significant (P<0.05) inhibition of cartilage damage when administered orally.
- MMP inhibitors reduced cartilage damage by 36-42%.
Conclusions:
- MMP inhibitors offer partial protection against cartilage and subchondral bone damage in this arthritis model.
- These results underscore the significant role of MMPs in mediating joint damage in iodoacetate-induced arthritis.
