Hyaluronic acid suppresses fibronectin fragment mediated cartilage chondrolysis: I. In vitro.
A commercial preparation of 800-kDa hyaluronic acid (HA), (ARTZ from Seikagaku, Inc.), has been used as a therapeutic intervention in the treatment of osteoarthritis (OA). We tested the effect of this HA form, HA/800, in an in vitro cartilage chondrolytic system in which a specific amino-terminal 29-kDa fragment of fibronectin (Fn-f) penetrates cartilage tissue to activate chondrocytes to amplify two major chondrolytic activities: suppression of proteoglycan (PG) synthesis and induction of matrix metalloproteinases. We report that HA/800 did not block damage by Fn-f in serum free cartilage cultures. However, HA/800 was effective in blocking the ability of 100 nM Fn-f to cause the degradation and release of half of the total cartilage PG from cartilage in 10% serum/DMEM cultures. While the Fn-f caused a half-time for PG release of 3 days, continuous exposure to 0.1 or 1 mg/ml HA/800 slowed the half-time to 12 days. Further, a single 1 day pre-incubation with 0.1 or 1 mg/ml HA/800 was sufficient to decrease the half-time of 100 nM Fn-f mediated PG depletion to 7 and 12 days, respectively. HA/800 completely blocked the effect of 10 nM Fn-f. Blocking of Fn-f-mediated cartilage PG depletion was associated with a decreased concentration of Fn-f on the superficial cartilage surface and decreased penetration into the cultured cartilage tissue. Further, the two major chondrolytic activities of the Fn-f, suppression of synthesis of PG and enhanced release of stromelysin-1, were suppressed by HA/800. HA/800 also partially restored PG in cartilage first damaged with the Fn-F. We conclude that HA/800 slows Fn-f-mediated cartilage chondrolysis in vitro and has some reparative potential. The damage blocking activity appears to be associated with the ability of HA/800 to block penetration of the Fn-f, rather than with direct effects on cartilage tissue.
Homandberg
G A
GA
Department of Biochemistry, Rush Medical College, Rush-Presbyterian-St. Luke's Medical Center, Chicago, Illinois 60612-3864, USA.
Hui
F
F
Wen
C
C
Kuettner
K E
KE
Williams
J M
JM
D000818:Animals; D019921:Biotinylation; D015153:Blotting, Western; D002358:Cartilage, Articular / Q000187:drug effects* / Q000378:metabolism; D002417:Cattle; D019902:Chondrocytes / Q000187:drug effects* / Q000378:metabolism; D016895:Culture Media, Serum-Free; D005353:Fibronectins / Q000037:antagonists & inhibitors* / Q000378:metabolism / Q000494:pharmacology; D006820:Hyaluronic Acid / Q000378:metabolism / Q000494:pharmacology*; D019278:Matrix Metalloproteinase 3 / Q000378:metabolism; D009924:Organ Culture Techniques; D010446:Peptide Fragments / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D011509:Proteoglycans / Q000378:metabolism; D013997:Time Factors
D016895:Culture Media, Serum-Free; D005353:Fibronectins; D010446:Peptide Fragments; D011509:Proteoglycans; D006820:Hyaluronic Acid; D019278:Matrix Metalloproteinase 3