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.
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.
Authors: György Dormán; Sándor Cseh; István Hajdú; László Barna; Dénes Kónya; Krisztina Kupai; László Kovács; Péter Ferdinandy Journal: Drugs Date: 2010-05-28 Impact factor: 9.546
Authors: Yun Ding; Heather O'Keefe; Jennifer L DeLorey; David I Israel; Jeffrey A Messer; Cynthia H Chiu; Steven R Skinner; Rosalie E Matico; Monique F Murray-Thompson; Fan Li; Matthew A Clark; John W Cuozzo; Christopher Arico-Muendel; Barry A Morgan Journal: ACS Med Chem Lett Date: 2015-07-07 Impact factor: 4.345
Authors: Peter-Martin Krarup; Mikkel Eld; Lars Nannestad Jorgensen; Mark Berner Hansen; Magnus S Ågren Journal: Int J Colorectal Dis Date: 2017-07-17 Impact factor: 2.571
Authors: Dorothea Piecha; Jürgen Weik; Heike Kheil; Gabriele Becher; Andreas Timmermann; Andreas Jaworski; Maren Burger; Michael W Hofmann Journal: Inflamm Res Date: 2009-11-10 Impact factor: 4.575
Authors: Stacey Fossey; John Vahle; Philip Long; Scott Schelling; Heinrich Ernst; Rogely Waite Boyce; Jacquelin Jolette; Brad Bolon; Alison Bendele; Matthias Rinke; Laura Healy; Wanda High; Daniel Robert Roth; Michael Boyle; Joel Leininger Journal: J Toxicol Pathol Date: 2016-07-29 Impact factor: 1.628