Hylan G-F 20 maintains cartilage integrity and decreases osteophyte formation in osteoarthritis through both anabolic and anti-catabolic mechanisms.

Abstract

OBJECTIVE:

To perform a molecular mechanism-based investigation of the chondroprotective potential of hylan G-F 20.

METHOD:

The effects of hylan G-F 20 on IL-1β-induced glycosaminoglycan (GAG) depletion and matrix metalloproteinase (MMP) expression in bovine and human cartilage explants were evaluated. Three weekly intra-articular hylan G-F 20 or control injections were administered 4 weeks post-operatively to rabbits with surgically induced osteoarthritis (OA). Cartilage histopathologic scores and osteophyte size were evaluated at 1, 4, and 8 weeks post-injections. Histomorphometry and immunostaining were used to quantify cartilage area and type II collagen (Col II) intensity, and real-time polymerase chain reaction (PCR) was used to examine the mRNA levels of Col2A1, MMP-13, -16 and IL-1β at 1 week.

RESULTS:

Hylan G-F 20 retained GAG in IL-1β-exposed bovine and human cartilage explants and abrogated IL-1β-mediated increases in MMP-1, -3, and -13 in human explant culture. Hylan G-F 20‒treated OA joints had significantly better cartilage integrity at 1 and 4 weeks post-treatment and significantly smaller osteophytes at 4 weeks compared with control. Col2A1 mRNA increased with hylan G-F 20 treatment, which correlated with a trend toward increased Col II immunostaining. MMP-13 and -16 mRNAs increased in OA cartilage, but were not significantly altered by hylan G-F 20. IL-1β mRNA was undetectable in cartilage and unaltered in the synovium.

CONCLUSIONS:

Hylan G-F 20 improved cartilage integrity and decreased osteophyte formation in the rabbit model of OA. Our results suggest that hylan G-F 20 may stimulate cartilage repair by increasing Col II, and inhibit IL-1β-mediated matrix degradation by decreasing MMPs.

• Authors: P Li, D Raitcheva, M Hawes, N Moran, X Yu, F Wang, G L Matthews
• Journal: Osteoarthritis and cartilage (Osteoarthritis Cartilage) Vol. 20 Issue 11 Pg. 1336-46 (Nov 2012) ISSN: 1522-9653 [Electronic] England
• PMID: 22809835 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2012. Published by Elsevier Ltd.

Chemical References

• Biocompatible Materials
• hylan
• Hyaluronic Acid

Topics

• Aged
• Animals
• Biocompatible Materials (pharmacology)
• Cartilage, Articular (drug effects, metabolism, pathology)
• Cattle
• Cells, Cultured
• Chondrocytes (drug effects, metabolism, pathology)
• Disease Models, Animal
• Humans
• Hyaluronic Acid (analogs & derivatives, pharmacology)
• Injections, Intra-Articular
• Male
• Osteoarthritis (drug therapy, metabolism, pathology)
• Osteophyte (chemically induced, metabolism, pathology)
• Rabbits