MMP-mediated collagen breakdown induced by activated protein C in equine cartilage is reduced by corticosteroids.
J Orthop Res
; 28(3): 370-8, 2010 Mar.
Article
in En
| MEDLINE
| ID: mdl-19777546
ABSTRACT
The plasma serine protease activated protein C (APC) is synthesized by human chondrocytes at sites of pathological cartilage fibrillation. APC levels are increased in osteoarthritis (OA) synovial fluid, and in vitro APC has been shown to synergize with interleukin-1beta (IL-1) to promote degradation from ovine cartilage. A model of equine cartilage degradation was established and used to explore corticosteroid activities. Intraarticular corticosteroids are a commonly prescribed treatment for joint disease, however their role in disease modification remains unclear. APC synergized with IL-1 or tumor necrosis factor-alpha (TNFalpha), promoting significant collagen degradation from equine cartilage explants within 4 days, but did not augment glycoaminoglycan (GAG) release. APC activated pro-matrix metalloproteinases (MMP)-2 but not pro-MMP-9, as assessed by gelatin zymography. APC did not directly activate pro-MMP-13. Dexamethasone, triamcinolone, and methylprednisolone acetate (MPA) were evaluated at concentrations between 10(- 5)M and 10(-10)M. High concentrations significantly increased GAG release from IL-1+APC-treated explants. With the exception of MPA at 10(-10)M, all concentrations of corticosteroids caused significant decreases in IL-1+APC-driven hydroxyproline loss. Treatment with corticosteroids suppressed expression of MMP-1, -3, and -13 mRNA. The collagenolysis associated with IL-1+APC synergy, and the inhibition of this effect by corticosteroids may involve gelatinase activation and downregulation of MMP expression, respectively.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Protein C
/
Triamcinolone
/
Cartilage
/
Collagen
/
Adrenal Cortex Hormones
/
Matrix Metalloproteinases
/
Serine Proteases
Type of study:
Prognostic_studies
Limits:
Animals
/
Humans
Language:
En
Journal:
J Orthop Res
Year:
2010
Document type:
Article
Affiliation country:
United kingdom