Related Experiment Video
Updated: Sep 25, 2026
Bacterial Expression and Purification of Human Matrix Metalloproteinase-3 using Affinity Chromatography
Published on: March 30, 2022
Broad-spectrum matrix metalloproteinase inhibitor marimastat-induced musculoskeletal side effects in rats
Richard Renkiewicz1, Luping Qiu, Charles Lesch
1Pfizer Global Research & Development Ann Arbor Laboratories, Pfizer, Inc, Ann Arbor, Michigan 48105, USA.
Objective:
To characterize the clinical and histopathologic changes in a rat model of broad-spectrum matrix metalloproteinase (MMP)-induced musculoskeletal syndrome (MSS), and to facilitate research into the causes and treatments of MSS in humans.
Methods:
Male Lewis rats weighing 150-180 gm were administered 10-30 mg of the broad-spectrum MMP inhibitor marimastat over a 2-week period via surgically implanted subcutaneous osmotic pumps. The animals were monitored and scored for the onset and severity of MSS, using clinical and histologic parameters.
Results:
Marimastat-treated rats exhibited various clinical signs, including compromised ability to rest on their hind feet, high-stepping gait, reluctance or inability to move, and hind paw swelling. Histologically, marimastat-treated rat joints were characterized by soft tissue and bone changes, such as increased epiphyseal growth plate, synovial hyperplasia, and increased cellularity in the joint capsule and extracapsular ligaments. The severity of MSS, as judged by clinical criteria (2 blinded observers using 3 clinical parameters), paw volume, and histologic score, was nearly identical. The observed changes were indistinguishable from those reported for primate models and mimic MSS in humans.
Conclusion:
This simple and sensitive model of MSS is an attractive alternative for studying the pathology of MSS.
Insights
A new rat model effectively mimics human musculoskeletal syndrome (MSS) by using a matrix metalloproteinase (MMP) inhibitor. This model shows clinical and histopathologic changes, offering a valuable tool for MSS research.
Area of Science:
- Biomedical research
- Animal modeling
- Pharmacology
Background:
- Musculoskeletal syndrome (MSS) poses a significant challenge in human health.
- Matrix metalloproteinases (MMPs) are implicated in various connective tissue disorders.
- Developing reliable animal models is crucial for understanding MSS pathogenesis and testing therapeutics.
Purpose of the Study:
- To establish and characterize a rat model of broad-spectrum matrix metalloproteinase (MMP)-induced musculoskeletal syndrome (MSS).
- To evaluate the clinical and histopathologic changes in this novel MSS model.
- To provide a research platform for investigating MSS causes and treatments.
Main Methods:
- Male Lewis rats were administered marimastat, a broad-spectrum MMP inhibitor, via subcutaneous osmotic pumps over two weeks.
- Animals were monitored for clinical signs of MSS, including gait abnormalities and paw swelling.
- Histopathologic analysis of joints assessed soft tissue and bone changes.
Main Results:
- Marimastat-treated rats displayed clinical signs consistent with MSS, such as impaired mobility and hind paw edema.
- Histological examination revealed increased epiphyseal growth plate, synovial hyperplasia, and joint capsule cellularity.
- Clinical and histological findings strongly correlated and mimicked MSS observed in primate models and humans.
Conclusions:
- A simple and sensitive rat model of MMP-induced MSS has been successfully developed.
- This model accurately replicates key features of human MSS, making it valuable for further research.
- The model serves as an attractive alternative for studying MSS pathology and evaluating potential treatments.
