Yonsei Med J.  2016 May;57(3):735-740. 10.3349/ymj.2016.57.3.735.

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

• Jian-lin Z
• Hong-song
• Hao P
• Shuang D
• Shen C
• Jian-ping
• Bo Q
• Jin-qing W
• Feng L

• KMID: 2374095
• DOI: http://doi.org/10.3349/ymj.2016.57.3.735

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 cartilage samples 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 replacement because 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 reaction and 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 expression of 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.

Keyword

HIF-2α; VEGF; cartilage degeneration; KL grade

MeSH Terms

Adult
Aged
Arthroplasty, Replacement, Knee
Arthroscopy
Basic Helix-Loop-Helix Transcription Factors/*metabolism
Biomarkers/*blood
Cartilage/*metabolism
Female
Humans
Knee Joint/*diagnostic imaging
Male
Middle Aged
Osteoarthritis, Knee/*blood/diagnostic imaging/physiopathology
RNA, Messenger
Radiography
Real-Time Polymerase Chain Reaction
Severity of Illness Index
Vascular Endothelial Growth Factor A/*metabolism
Basic Helix-Loop-Helix Transcription Factors
Biomarkers
RNA, Messenger
Vascular Endothelial Growth Factor A

Figure

• 

  Fig. 1 (A) Representative sections of cartilage from the femoral condyles (H&E staining). a: KL grade 0 group present normal cartilage with no evident changes; b: KL grade 2 group showing mild loss of height of articular cartilage; c and d: KL grade 3 and 4 groups increased flaking of cartilage, clefts deep to the radial zone, loss of coumnization of cellular distribution, and increased areas of hypocellularity. (B) Representative sections of cartilage from the femoral condyles (safranin-O staining). a: KL grade 0 group cartilage of normal showing anintact profile, and there is no evident loss of proteoglycan (PGs); b: KL grade 2 group showing light changes of PGs loss; c and d: KL grade 3 and 4 groups showing severe loss of PGs, and clefts deep to the radial zone. (C) The correlation between Mankin's score and KL grades (r=0.8790, p<0.01). KL, Kellgren and Lawrence; H&E, hematoxylin and eosin.

• 

  Fig. 2 HIF-2α mRNA levels exhibited a positive correlation with radiographic severity of knee OA (r=0.7001, p<0.05); VEGF level was correlated with the radio-graphic severity (r=0.6647, p<0.05). HIF-2α, hypoxia-inducible factor-2; OA, osteoarthritis; VEGF, vascular endothelial growth factor; KL, Kellgren and Lawrence; GAPDH, glyceraldehyde phosphate dehydrogenase.

• 

  Fig. 3 The expression of HIF-2α and VEGF protein were measured by Western blotting, and there were liner increased with the radio-graphic severity. HIF-2α, hypoxia-inducible factor-2; VEGF, vascular endothelial growth factor; KL, Kellgren and Lawrence; GAPDH, glyceraldehyde phosphate dehydrogenase.

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