Arthritic disease suppression and cartilage protection with glycosaminoglycan polypeptide complexes (Peptacans) derived from the cartilage extracellular matrix: A novel approach to therapy

Ghosh, P., Shimmon, S. and Whitehouse, M. W. (2006) Arthritic disease suppression and cartilage protection with glycosaminoglycan polypeptide complexes (Peptacans) derived from the cartilage extracellular matrix: A novel approach to therapy. Inflammopharmacology, 14 3-4: 161-168.


Author Ghosh, P.
Shimmon, S.
Whitehouse, M. W.
Title Arthritic disease suppression and cartilage protection with glycosaminoglycan polypeptide complexes (Peptacans) derived from the cartilage extracellular matrix: A novel approach to therapy
Journal name Inflammopharmacology  (ERA 2012 Listed)    (ERA 2010 Rank B)   Check publisher's open access policy
Publication date 2006-08
Sub-type Article
DOI 10.1007/s10787-006-1522-8
Volume number 14
Issue number 3-4
ISSN 0925-4692
Start page 161
End page 168
Total pages 8
Editor K. D. Rainsford
Place of publication Basel, Switzerland
Publisher Birkhauser
Collection year 2006
Language eng
Subject C1
320503 Clinical Pharmacology and Therapeutics
730305 Diagnostic methods
1115 Pharmacology and Pharmaceutical Sciences
Abstract Molecular fragments of cartilage are antigenic and can stimulate an autoimmune response. Oral administration of type II collagen prevents disease onset in animal models of arthritis but the effects of other matrix components have not been reported. We evaluated glycosaminoglycan polypeptides (GAG-P) and matrix proteins (CaP) from cartilage for a) mitigating disease activity in rats with collagen-induced arthritis (CIA) and adjuvant-induced arthritis (AIA) and b) stimulating proteoglycan (PG) synthesis by chondrocytes in-vitro. CIA and AIA were established in Wistar rats using standard methods. Agents were administered orally (10–200 mg/kg), either for seven days prior to disease induction (toleragenic protocol), or continuously for 15 days after injecting the arthritigen (prophylactic protocol). Joint swelling and arthritis scores were determined on day 15. Histological sections of joint tissues were assessed post-necropsy. In chondrocyte cultures, CaP + / − interleukin-1 stimulated PG biosynthesis. CaP was also active in preventing arthritis onset at 3.3, 10 or 20 mg/kg in the rat CIA model using the toleragenic protocol. It was only active at 20 and 200 mg/kg in the CIA prophylactic protocol. GAG-P was active in the CIA toleragenic protocol at 20 mg/kg but chondroitin sulfate and glucosamine hydrochloride or glucosamine sulfate were all inactive. The efficacy of CaP in the rat AIA model was less than in the CIA model. These findings lead us to suggest that oral CaP could be used as a disease-modifying anti-arthritic drug.
Keyword Cartilage
CaPeptacan glycosaminoglycans
Matrix proteins
Arthritis models
Chondroprotection
Q-Index Code C1

 
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Created: Wed, 15 Aug 2007, 09:59:08 EST