Effects of hyaluronan on vascular endothelial growth factor and receptor-2 expression in a rabbit osteoarthritis model.
BACKGROUND
Little is known about the expression of vascular endothelial growth factor (VEGF) and its receptor-2 (VEGFR-2) mRNA in the cartilage of a rabbit osteoarthritis model or the influence of intraarticular injection of hyaluronan (HA) on the expression of VEGF and VEGFR-2 in cartilage during the process of osteoarthritis (OA). The therapeutic mechanism of HA is not completely understood, and we hypothesize that the mechanism is through the effects of VEGF and VEGFR2. In this study, we determined the VEGF and VEGFR-2 mRNA expression in a rabbit OA model and assessed the therapeutic mechanism of HA against OA.


METHODS
We carried out this study at the Center Laboratory of Renmin Hospital at Wuhan University and the Key Laboratory of Respiratory Disease of the Ministry of Public Health, Huazhong University of Science and Technology. Between October 2006 and April 2008 a total of 24 mature New Zealand white rabbits were divided into three groups: normal controls, a no-HA group, and an HA group. The no-HA and HA groups underwent unilateral anterior cruciate ligament transection. At 4 weeks after the operation, animals in the HA group received intraarticular injections of 1% sodium hyaluronate (HA) once a week for 5 weeks as per the clinical treatment presently utilized. The no-HA rabbits were not given HA. At death, 11 weeks following surgery, cartilage was harvested and total RNA was extracted. VEGF and VEGFR mRNAs were analyzed using the reverse transcription-polymerase chain reaction (RT-PCR) and real-time PCR for each group.


RESULTS
Cartilage damage (both extent and grade) was less severe in the HA group than in the no-HA group. VEGF and VEGFR-2 mRNA expression was enhanced in the cartilage of the OA model. Intraarticular 1% sodium hyaluronate injection inhibited VEGFR-2 expression but had no effect on reducing the VEGF mRNA expression in cartilage.


CONCLUSIONS
These results suggested that VEGF and VEGFR-2 may be involved in the progression of OA and in the therapeutic mechanism of HA at least partly through the influence of VEGFR-2 expression during the development of OA.
Zhou
Jian-lin
JL
Department of Orthopedics, Renmin Hospital of Wuhan University, Wuhan 430060, Hubei Province, People's Republic of China.
Liu
Shi-qing
SQ
Qiu
Bo
B
Hu
Qiong-jie
QJ
Ming
Jiang-hua
JH
Peng
Hao
H
D000818:Animals; D002358:Cartilage, Articular / Q000187:drug effects* / Q000378:metabolism; D015536:Down-Regulation; D006820:Hyaluronic Acid / Q000494:pharmacology*; D010003:Osteoarthritis / Q000188:drug therapy* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D011817:Rabbits; D020133:Reverse Transcriptase Polymerase Chain Reaction; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000235:genetics / Q000378:metabolism*; D055675:Viscosupplements / Q000494:pharmacology*
D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; D055675:Viscosupplements; D006820:Hyaluronic Acid; D040301:Vascular Endothelial Growth Factor Receptor-2