The effect of HIF stabilizer on distraction osteogenesis

Abstract

Objective: The aim of this study was to investigate the effect of an orally applicable hypoxia-inducible factor (HIF) stabilizer on distraction osteogenesis (DO) in a rat model.

Methods: The study included 24 Wistar albino rats undergoing osteotomy of the left tibia diaphysis. Rats were divided equally into experiment and control groups. Tibias were fixed using an external fixator. HIF stabilizer was administered to the experiment group. On the 5th postoperative day, distraction with increased rate (0.4 mm twice a day) was commenced and continued for 10 days. Histological and immunohistochemical evaluation was performed.

Results: Vascular endothelial growth factor levels of the experiment group were higher than those of the control group (p<0.05). The experiment group had slightly better intramembranous ossification quality than the control group on both Day 16 and 30. Endochondral ossification rates were better in the experiment group on Day 16.

Conclusion: Vascular endothelial growth factor levels increased and stimulated angiogenesis in the presence of HIF pathway activation by oral administration of HIF stabilizer during DO. The biomechanical features of the distraction and angiogenesis should be coupled to achieve adequate bone homeostasis.

Keywords

• Angiogenesis
• distraction osteogenesis
• HIF stabilizer
• VEGF

Distraksiyon osteogenezinde HİFstabilizasyonunun etkisi

Abstract

Amaç: Çalışmamızda sıçandaki distraksiyon osteogenezi (DO) modelinde oral olarak uygulanabilen hipoksi ile indüklenebilir faktörün (HİF) etkisinin incelemeyi amaçladık.

Çalışma planı: Çalışmada sol tibia diyafizine osteotomi uygulanan 24 Wistar albino sıçan kullanıldı. Denekler deney ve kontrol olmak üzere iki gruba ayrıldı. Eksternal fiksatör ile tespit sağlanarak, deney grubuna HİF stabilizatörü verildi. Cerrahi sonrası 5. günlük latent dönemi takiben, 10 gün boyunca hızlandırılmış distraksiyon (günde iki kez 0.4 mm) uygulandı. Histolojik ve immünohistokimyasal değerlendirmeler yapıldı.

Bulgular: Deney grubundaki vasküler endotelial büyüme faktörü (VEBF) düzeyi kontrol grubuna kıyasla daha yüksek idi (p<0.05). Deney grubundaki intramembranöz ossifikasyon oranının 16. ve 30. günlerde kontrol grubuna göre bir miktar daha yüksek olduğu gözlendi. Yine deney grubundaki endokondral ossifikasyon miktarının 16. günde daha yüksek olduğu bulundu.

Çıkarımlar: Hipoksi ile indüklenebilir faktör stabilizatörünün oral olarak uygulanması ile DO sıra¬sında VEBF düzeylerinin yükselerek HİF yolağının aktive olması sonucu anjiyogenezin uyarıldığını gösterdik. İyi bir kemik oluşumu için distraksiyona ait biyomekanik faktörler ve anjiyogenezin eşleş¬mesi gereklidir.

Keywords

• Anjiyogenez; distraksiyon osteogenezi; HİF stabilizatörü; VEBF.

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