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Human Scaphoid Non-unions Exhibit Increased Osteoclast Activity Compared To Adjacent Cancellous Bone
Bjorn Behr, MD; Matthias Schulte, PhD; Döbele Carmen, MD; Christoph Wallner, MD; Kneser Ulrich, MD; Lehnhardt Marcus, MD; Schira Jessica, MD
BG Trauma Center Ludwigshafen/ University of Heidelberg, Ludwigshafen, Germany

Scaphoid bones 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 the present study, gene expression of osteogenic and angiogenic growth and transcription factors as well as inflammatory mediators were analyzed in human scaphoid non-unions and intraindividually compared to adjacent autologous cancellous bone from the distal radius. In addition, histology and immunohistochemical stainings were performed to verify qRT-PCR data. Gene expression analysis revealed a significant upregulation of TNF-α, RANKL, ALP, CYCLIN D1, MMP-13, OPG, NFATc1, TGF-α and WNT5A in scaphoid non-unions. Interestingly, TNF-ŕ was highly upregulated in all non-union samples (mean: 26 fold increase). Moreover, RANKL, a marker for osteoclastogenesis was increased by 20 folds in non-unions. TRAP staining confirmed this observation. 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. Importantly, we did not detect differences in angiogenesis between scaphoid non-unions and controls in both gene expression and immunohistochemistry. Summarized, our data indicate chronic inflammation and increased osteoclast activity in scaphoid non-unions. These data increase our understanding for the reduced bone regeneration capacity present in scaphoid non-unions and may translate into identification of new therapeutic targets in order to avoid secondary damages and prevent occurrence of non-unions to scaphoid bones.

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