Artikel
Tnf-alpha and osteoclastogenesis is upregulated in human scaphoid non-unions in comparison to cancellous bone from the distal radius
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Veröffentlicht: | 24. April 2015 |
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Introduction: The scaphoid bone has the highest prevalence for non-union in the human body. Even with adequate treatment, bone regeneration does not occur in many instances. Although this condition is well described, the molecular pathology of scaphoid non-unions is still poorly defined.
Material and methods: In this project, gene expression of osteogenic, inflammatory and angiogenic growth and transcription factors was analyzed in human scaphoid non-unions and compared to adjacent autologous cancellous bone from the distal radius in 72 patients. In addition, histology and immunohistochemistry was performed.
Results: Our data show a significant upregulation of TNF-a, RANKL and WNT5a in scaphoid non-unions, indicating chronic inflammation and increased osteoclast activity. Interestingly, TNF-a was highly upregulated in all samples (mean: 9.7 fold upregulation, SEM: 10.5). In addition, markers for acute inflammation such as IL-1β or IFN-γ were not detectable in neither tissue. With respect to genes related to osteogenesis, alkaline phosphatase was significantly upregulated in scaphoid non-unions. No differences were detectable for other osteogenic genes such as RUNX-2 or BMP-2. To our surprise, we did not find differences in angiogenesis between the scaphoid non-unions and control bone. TRAP staining and immunohistochemistry data confirmed these observations.
Conclusion: Summarized, our data show a dramatic upregulation of TNF-a and genes involved in osteoclastogenesis in scaphoid non-unions. These data can increase our understanding for the reduced bone regeneration capacity present in scaphoid non-unions and may translate into the identification of new therapeutic targets in order to avoid secondary damages and prevent occurrence of non-unions to scaphoid bones.