Analysis of absent bone regeneration after occupational injuries in scaphoid non-unions

Status:

completed 10/2014

Aims:

Scaphoid bones remain to have a high prevalence for non-union. Even with adequate treatment, bone regeneration may not occur in certain instances. Although this condition is well described, the molecular pathology of scaphoid non-unions is still poorly defined.

Activities/Methods:

In this project, gene expression of osteogenic, inflammatory and angiogenic growth and transcription factors were analyzed in human scaphoid non-unions and compared to adjacent autologous cancellous bone from the distal radius. 84 patients were recruited for the study. In addition, histology, immunohistochemistry and in vitro experiments were performed.

Results:

Our gene expression data show a significant upregulation of TNF-α, RANKL, ALP, CYCLIN D1, MMP-13, OPG, NFATc1, TGF-β and WNT5a in scaphoid non-unions, indicating chronic inflammation and increased osteoclast activity. Interestingly, TNF-α was highly upregulated in all non-union samples (mean: 25 fold increase). Moreover, RANKL, a marker for osteoclastogenesis was increased by 20 fold in non-unions. However, markers for acute inflammation such as IL-1β or IFN-γ were not detectable in both tissues. 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 detect differences in angiogenesis between scaphoid non-unions and control bone. TRAP staining and immunohistochemistry data confirmed these observations. Summarized, our data show a dramatic upregulation of several genes in scaphoid non-unions, particularly TNF-α and RANKL. Moreover, scaphoid non-unions remain to have a potential for regeneration and do not show alteration in angiogenesis as compared to control tissue. These data 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.

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