Fibroblast growth factor-18 stimulates chondrogenesis and cartilage repair in a rat model of injury-induced osteoarthritis.
OBJECTIVE
Osteoarthritis (OA) is the most common form of arthritis and a primary cause of disability, however, there are no treatments that can slow disease progression or repair damaged joint cartilage. Fibroblast growth factor-18 (FGF18) has been reported to have significant anabolic effects on cartilage. We therefore examined its effects on repair of cartilage damage in a rat meniscal tear model of OA.


METHODS
Surgical damage to the meniscus in rats leads to joint instability and significant damage to the articular cartilage at 3 weeks post-surgery. At this time, animals received bi-weekly intra-articular injections of FGF18 for 3 weeks, and the knee joints were then harvested for histologic examination.


RESULTS
FGF18-induced dose-dependent increases in cartilage thickness of the tibial plateau, due to new cartilage formation at the articular surface and the joint periphery. The generation of new cartilage resulted in significant reductions in cartilage degeneration scores. The highest dose of FGF18 also induced an increase in chondrophyte size and increased remodeling of the subchondral bone.


CONCLUSIONS
The results of this study demonstrate that FGF18 can stimulate repair of damaged cartilage in a setting of rapidly progressive OA in rats.
Moore
E E
EE
ZymoGenetics, Inc., 1201 Eastlake Avenue East, Seattle, WA 98102, USA.
Bendele
A M
AM
Thompson
D L
DL
Littau
A
A
Waggie
K S
KS
Reardon
B
B
Ellsworth
J L
JL
D000818:Animals; D002358:Cartilage, Articular / Q000187:drug effects* / Q000473:pathology; D019902:Chondrocytes / Q000378:metabolism*; D020219:Chondrogenesis / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D005346:Fibroblast Growth Factors / Q000008:administration & dosage* / Q000627:therapeutic use; D008297:Male; D010003:Osteoarthritis / Q000503:physiopathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014945:Wound Healing / Q000187:drug effects
C113569:fibroblast growth factor 18; D005346:Fibroblast Growth Factors