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Updated: May 5, 2026
Development and Evaluation of a Rat Model of Full-Thickness Cartilage Defects
Published on: May 19, 2023
Statins and fibrates do not affect development of spontaneous cartilage damage in STR/Ort mice
W Wei1, S Clockaerts2, Y M Bastiaansen-Jenniskens1
1Department of Orthopaedics, Erasmus MC University Medical Center, Rotterdam, The Netherlands.
Objective:
Since statins and fibrates are capable of improving the metabolic profile of patients as well as decreasing inflammation, they are considered as potential drugs for preventing osteoarthritis (OA). The goal of the present study was to investigate the effect of these drugs in the STR/Ort spontaneous OA mouse model.
Design:
Male STR/Ort mice received control diet or control diet containing two different dosages of simvastatin or fenofibrate or a combination of both. Mice were euthanized after 16 weeks of treatment at the age of 24 weeks. Serum analysis for metabolic and inflammatory markers, histologic OA grading and micro computed tomography (μCT) analysis of subchondral bone plate were performed.
Results:
Simvastatin treatment did not have a statistically significant effect on any of the measured parameters. Fenofibrate treated mice gained less body weight (BW) and had lower serum amyloid A (SAA) levels, but higher Interleukin (IL)-1α and MIP1α than other mice. Mice treated with 200 mg/kg BW/day fenofibrate had less subchondral bone plate volume than control, but no statistically significant reduction in cartilage damage. In the combination treatment group, BW and SAA were lower than control. Overall, bodyweight, synovium membrane cell layers and SAA levels correlated to subchondral bone plate changes and subchondral bone plate changes correlated to cartilage damage.
Conclusions:
Statins and fibrates did not affect development of cartilage damage in the STR/Ort spontaneous OA mouse model. Fenofibrates however, had an effect on BW, serum inflammation markers and subchondral bone plate morphology.
Insights
Statins and fibrates did not prevent osteoarthritis (OA) development in mice. Fenofibrates affected body weight, inflammation markers, and bone structure, but not cartilage damage in this OA model.
Area of Science:
- Biochemistry
- Pharmacology
- Orthopedics
Background:
- Osteoarthritis (OA) is a degenerative joint disease with limited treatment options.
- Statins and fibrates are known to improve metabolic profiles and reduce inflammation, suggesting potential OA therapeutic benefits.
- The STR/Ort mouse model spontaneously develops OA, making it suitable for investigating preventative strategies.
Purpose of the Study:
- To evaluate the efficacy of simvastatin and fenofibrate, alone or in combination, in preventing osteoarthritis development.
- To assess the impact of these drugs on metabolic and inflammatory markers, cartilage integrity, and subchondral bone structure in the STR/Ort mouse model.
Main Methods:
- Male STR/Ort mice were administered control diet, simvastatin, fenofibrate, or a combination for 16 weeks.
- Serum analysis included metabolic and inflammatory markers (e.g., SAA, IL-1α, MIP1α).
- Histological grading assessed cartilage damage, and micro-computed tomography (μCT) analyzed subchondral bone plate morphology.
Main Results:
- Simvastatin showed no significant effect on OA parameters.
- Fenofibrate treatment led to reduced body weight and lower serum amyloid A (SAA) levels, but increased Interleukin (IL)-1α and MIP1α.
- While fenofibrate altered subchondral bone plate volume, it did not significantly reduce cartilage damage. Combination therapy also lowered body weight and SAA.
- Correlations were observed between body weight, SAA levels, synovium cell layers, subchondral bone plate changes, and cartilage damage.
Conclusions:
- Neither statins nor fibrates demonstrated a preventive effect on cartilage damage in the STR/Ort spontaneous OA mouse model.
- Fenofibrates influenced body weight, serum inflammatory markers, and subchondral bone plate morphology, but not OA progression.
- Further research is needed to explore the complex interplay between metabolic factors, inflammation, bone structure, and cartilage degeneration in OA.
