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.
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.
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.
-cross sectoral-Type of hazard:
rehabilitationDescription, key words:
bone regeneration, scaphoid, carpus, pseudarthrosis