The Relationship between HIF-2α and VEGF with Radiographic Severity in the Primary Osteoarthritic Knee

다국어 초록 (Multilingual Abstract)

Purpose: The aim of this study was to determine the relationship of hypoxia-inducible factor-2 (HIF-2α) and vascular endothelial growth factor (VEGF) with radiographic severity in primary osteoarthritis (OA) of the knee. Expression of these two factors in cartilagesamples from OA knee joints was examined at mRNA and protein levels.
Materials and Methods: Knee joints were examined using plain radiographs, and OA severity was assessed using the Kellgren and Lawrence (KL) grading system. Specimens were collected from 29 patients (31 knees) who underwent total knee replacementbecause of severe medial OA of the knee (KL grades 3 and 4), 16 patients who underwent knee arthroscopy (KL grade 2), and 5 patients with traumatic knees (KL grade 0). HIF-2α and VEGF expression was quantified by real-time polymerase chain reactionand western blotting.
Results: Cartilage degeneration correlated with the radiographic severity grade. OA severity, determined using the Mankin scale, correlated positively with the KL grade (r=0.8790, p<0.01), and HIF-2α and VEGF levels with the radiographic severity of knee OA (r=0.7001, p<0.05; r=0.6647, p<0.05).
Conclusion: In OA cartilage, HIF-2α and VEGF mRNA and protein levels were significantly and positively correlated. The expressionof both factors correlated positively with the KL grade. HIF-2α and VEGF, therefore, may serve as biochemical markers as well as potential therapeutic targets in knee OA.

참고문헌 (Reference)

1 Enomoto H, "Vascular endothelial growth factor isoforms and their receptors are expressed in human osteoarthritic cartilage" 162 : 171-181, 2003

2 Pfander D, "Vascular endothelial growth factor in articular cartilage of healthy and osteoarthritic human knee joints" 60 : 1070-1073, 2001

3 Gerber HP, "VEGF couples hypertrophic cartilage remodeling, ossification and angiogenesis during endochondral bone formation" 5 : 623-628, 1999

4 Saito T, "Transcriptional regulation of endochondral ossification by HIF-2alpha during skeletal growth and osteoarthritis development" 16 : 678-686, 2010

5 Horner A, "Tie2 ligands angiopoietin-1 and angiopoietin-2 are coexpressed with vascular endothelial cell growth factor in growing human bone" 28 : 65-71, 2001

6 Pufe T, "The splice variants VEGF121 and VEGF189 of the angiogenic peptide vascular endothelial growth factor are expressed in osteoarthritic cartilage" 44 : 1082-1088, 2001

7 Chen XY, "The effect of vascular endothelial growth factor on aggrecan and type II collagen expression in rat articular chondrocytes" 32 : 3359-3364, 2012

8 Saetan N, "Relationship of plasma and synovial fluid vascular endothelial growth factor with radiographic severity in primary knee osteoarthritis" 38 : 1099-1104, 2014

9 Kellgren JH, "Radiological assessment of osteo-arthrosis" 16 : 494-502, 1957

10 Sharma L, "Osteoarthritis: Diagnosis and Medical/Surgical Management" Wolters Kluwer/Lippincott Williams & Wilkins 3-26, 2007

11 Hunter DJ, "Osteoarthritis" 332 : 639-642, 2006

12 Ryu JH, "Hypoxia-inducible factor-2α regulates Fas-mediated chondrocyte apoptosis during osteoarthritic cartilage destruction" 19 : 440-450, 2012

13 Yang S, "Hypoxia-inducible factor-2alpha is a catabolic regulator of osteoarthritic cartilage destruction" 16 : 687-693, 2010

14 Saito T, "HIF-2α as a possible therapeutic target of osteoarthritis" 18 : 1552-1556, 2010

15 Zhou JL, "Effects of hyaluronan on vascular endothelial growth factor and receptor-2 expres-sion in a rabbit osteoarthritis model" 14 : 313-319, 2009

16 Mankin HJ, "Biochemical and metabolic abnormalities in articular cartilage from osteo-arthritic human hips. II. Correlation of morphology with biochemical and metabolic data" 53 : 523-537, 1971