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Collagenase‐3 derived peptide inhibitor is chondro‐protective in a rat model of osteoarthritis
Author(s) -
Holmes Tiffany C,
Lau Shukkwan K,
Youngwirth Jonathan,
Klunk James,
Lombard Frederick J,
Earland Noah,
Pinkney Nathaniel,
Palumbo Dante,
Rutkowski Lorrine,
Denzine Mark,
Kubinski Andrew,
Maugle Tyson,
Lukashova Lyudamila,
Teixeira Cristina,
Selim Abdulhafez A,
D'Angelo Marina
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.lb46
Subject(s) - osteoarthritis , matrix metalloproteinase , collagenase , medicine , extracellular matrix , peptide , pathology , chemistry , biochemistry , enzyme , alternative medicine
Osteoarthritis (OA) is a disease of the joints caused by an imbalance between extracellular matrix destruction and production. Some of the molecular components responsible for this imbalance are matrix metalloproteinases (MMPs), especially, collagenase‐3 (MMP13) which degrades collagen type II. We have tested the efficacy of an MMP13‐derived peptide inhibitor (PxTx001‐1) in altering the pathology of an established rat model of OA. Utilizing the peptide as an early intervention therapeutic, we have assessed the ability of our inhibitor to affect the progress of OA. Peptide or control saline was injected into the OA knee joint for four consecutive weeks. Endpoint assessment of: toxicity, measured by CBC and serum chemistry; joint space narrowing, measured by X‐ray; joint functionality, measured by stride test; and tissue pathology, measured by micro computed tomography and histology were completed. All data indicates that the inhibitor is non‐toxic and diminishes the pathology associated with OA. We are currently testing this inhibitor's disease modifying properties in a canine model of OA. This work was supported, in part, by intramural funding.