1. Depletion of Perlecan HSDepletion of Perlecan HS
Reduces Cartilage DegradationReduces Cartilage Degradation
and Osteophyte Development inand Osteophyte Development in
Post-Traumatic OsteoarthritisPost-Traumatic Osteoarthritis
Cindy ShuCindy Shu, Christopher Little, James Melrose, Christopher Little, James Melrose
Raymond Purves Bone and Joint Research LaboratoryRaymond Purves Bone and Joint Research Laboratory
Kolling Institute of Medical ResearchKolling Institute of Medical Research
University of SydneyUniversity of Sydney
Royal North Shore Hospital, St Leonards 2065Royal North Shore Hospital, St Leonards 2065
Sydney, AustraliaSydney, Australia
Provided by: Cindy ShuProvided by: Cindy Shu

2. • In cartilage, perlecan domain I heparan sulfate has shown roles inIn cartilage, perlecan domain I heparan sulfate has shown roles in
FGF-2/18 signalingFGF-2/18 signaling
• Perlecan domain I heparan sulfate deficient mice (perlecan exon 3Perlecan domain I heparan sulfate deficient mice (perlecan exon 3
null) demonstrated reduced cartilage erosion and osteophytenull) demonstrated reduced cartilage erosion and osteophyte
formation in DMM-induced osteoarthritis compared to wildtypeformation in DMM-induced osteoarthritis compared to wildtype
counterpartcounterpart
• FGF-18 rather than FGF-2 showed protective role in cartilageFGF-18 rather than FGF-2 showed protective role in cartilage inin
vitrovitro, inhibited IL-1 induced glycosylaminoglycan release and, inhibited IL-1 induced glycosylaminoglycan release and
Mmp2Mmp2 gene expressiongene expression
• Inhibition of OA cartilage degradation in perlecan exon-3-null miceInhibition of OA cartilage degradation in perlecan exon-3-null mice
maybe associated with enhanced FGF-18 signaling in absence ofmaybe associated with enhanced FGF-18 signaling in absence of
perlecan domain I HSperlecan domain I HS
Provided by: Cindy Shu