Bilaterally increased VEGF‐levels in muscles during experimental unilateral callus distraction

Abstract

Angiogenesis is essential for wound healing and proliferative processes such as bone formation and repair. Since increased expression of the vascular endothelial growth factor (VEGF) stimulates bone formation, it can be hypothesized that surgical procedures leading to a systemic increase of VEGF for instance during wound healing, influence enchondral ossification processes and might be responsible for observed growth phenomena during callus distraction. To study the mechanisms of angiogenesis in soft tissue during unilateral callus distraction, lengthening of the right tibia was performed in 12 beagles. After osteotomy, application of a ring fixator and after five latency days, distraction was started for 25 days. A control group of four additional beagles underwent no surgical procedure. Subsequent to the distraction period (Group A), muscle samples from six beagles were taken from the distracted side (ds) and the contralateral non-distracted side (n-ds), six beagles underwent an additional consolidation period of 25 days (Group B). Samples were analyzed for VEGF, VEGFR-1 and VEGFR-2 mRNA expression using real-time PCR and protein expression using Western Blot analysis. Muscles from both extremities showed significantly increased expression of VEGF and its cognate receptors VEGFR-112. Expression decreased significantly after the consolidation period, whereby the level at the nondistracted side decreased more than the level at the distracted side. Interestingly VEGF and VEGFR-I levels at the non-distracted side were significantly higher than at the distracted side. In contrast VEGFR-2, the receptor that mediates endothelial cell proliferation, showed higher levels at the distracted than at the non-distracted side. These findings indicate that callus distraction results not only in locally increased expression of VEGF and its receptors, but leads also to increased VEGF and VEGFR-112 levels at distant sides and might therefore be responsible for the observed growth phenomena during callus distraction.

Distraction Osteogenesis Enhances Remodeling of Remote Bones of the Skeleton: A Pilot Study

“…In our study, a 10-day tibial distraction produced a measurable systemic anabolic effect on bone remodeling when compared to the values measured during the following consolidation phase in the same animals ( Table 1). The results of this experiment confirm previously performed studies examining the systemic influence of local skeletal injury [3,4,8,10,12,16,24,25,32] (Table 2). Our results demonstrate the quick onset of systemic stimulation of bone metabolism.…”

Microcirculation of secondary bone tumors in vivo: The impact of minor surgery at a distal site

“…However, the effect on established tumors remains widely unknown. Release of growth factors such as vascular endothelial growth factor (VEGF) plays an important role in maintenance of angiogenesis during wound healing subsequent to surgical trauma7 and has been demonstrated to have systemic effects at distant sites on tumor growth and other tissues 8–10. In this context surgery‐related modulation of angiogenic factors has been proposed to influence this balance and might therefore contribute to an acceleration of tumor growth at a distal site through alterations of the tumor microcirculation 3, 9…”

Angiogenesis and myogenesis in mouse tibialis anterior muscles during distraction osteogenesis: VEGF, its receptors, and myogenin genes expression

“…In skeletal muscles, VEGF activated angiogenesis in response to various stimulations, such as exercise and electrical stimulation. [23][24][25][26][27][28] Hansen-Algenstaedt et al 29 showed that distraction osteogenesis is sufficient to significantly increase the expression of VEGF, VEGFR-1, and VEGFR-2 at only two time points in beagle skeletal muscle. However, they did not examine the correlation between these molecules nor did they look at their effects on angiogenesis and myogenesis.…”