Hylan G-F 20 maintains cartilage integrity and decreases osteophyte formation in osteoarthritis through both anabolic and anti-catabolic mechanisms.
OBJECTIVE
To perform a molecular mechanism-based investigation of the chondroprotective potential of hylan G-F 20.


METHODS
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.
Department of Orthopaedic Research, Genzyme Corporation, Framingham, MA 01701, USA. ping.li@medtronic.com
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P
Li
D
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Raitcheva
M
M
Hawes
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N
Moran
X
X
Yu
F
F
Wang
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GL
Matthews
D000368:Aged; D000818:Animals; D001672:Biocompatible Materials / Q000494:pharmacology*; D002358:Cartilage, Articular / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D002417:Cattle; D002478:Cells, Cultured; D019902:Chondrocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D006801:Humans; D006820:Hyaluronic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D007270:Injections, Intra-Articular; D008297:Male; D010003:Osteoarthritis / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D054850:Osteophyte / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D011817:Rabbits
D001672:Biocompatible Materials; C049816:hylan; D006820:Hyaluronic Acid