Mandibular Distraction Osteogenesis and the Role of PTH- Molecular Mechanisms

Objectives: The objective of this study was to investigate gene responses of bone formation during osteodistraction, and to compare these responses to those obtained from the PTH stimulation. The hypothesis was that gene expression would be enhanced during osteodistraction and PTH administration.

Methods: Surgery was performed on 28 rat mandibles for gene analysis, with 7 rats placed into each of 4 groups: Group I- no distraction, no PTH; Group II- distraction only; Group III- PTH only; Group IV- PTH and distraction. The PTH (120 micro-grams/kg) was administered daily, via tail veins. Mandibular tissues were harvested immediately following the distraction period (no consolidation period). mRNA was extracted and purified. Reverse transcription was performed and real-time PCR was used to quantify specific bone biomarkers. ANOVA was used to analyze statistics. An additional five rats (Group V) underwent osteodistraction, similar to Group II, but were kept alive for another four weeks for histological study of bone formation.

Results: Bone biomarkers such as Cbfa1, BMP2, COLI, and ALP, involved in upregulation of osteoblastic differentiation, were seen in higher levels in the osteodistraction group (II) than in Group I. The PTH only group (III) showed downregulation of gene expression compared to Group I. Possibly the high dose of PTH used caused a catabolic effect.

Conclusion: PTH appeared to suppress gene expression synergistically when used with osteodistraction, giving Group IV the lowest gene expression levels. Histology and micro-CT showed approximately 45% new bone formation in Group V. Currently, we are investigating low dose PTH (60 micro-grams/kg) and the preliminary histological data shows an anabolic effect for callus formation. This model can be further used to assess other osteogenic therapy such as tissue engineering enhanced bone regeneration. (Supported in part by AAOF, UNC Dental School)