Human scaphoid non‐unions exhibit increased osteoclast activity compared to adjacent cancellous bone

Journal of Cellular and Molecular Medicine

Jessica Schira¹  Matthias Schulte²  Carmen Döbele²  Christoph Wallner¹  Stephanie Abraham¹  Adrien Daigeler¹  Ulrich Kneser²  Marcus Lehnhardt¹ 

[1] Department of Plastic Surgery, BG University Hospital Bergmannsheil, Ruhr University Bochum, Bochum, Germany;Department of Plastic Surgery, BG Trauma Hospital Ludwigshafen, University of Heidelberg, Ludwigshafen, Germany

关键词: non‐union;    osteoclasts;    scaphoid;    RANKL;    WNT5A;   

DOI  :  10.1111/jcmm.12677

来源: Wiley

【 摘 要 】

Abstract

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 this study, gene expression of osteogenic and angiogenic growth and transcription factors as well as inflammatory mediators were analysed 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 up-regulation of RANKL, ALP, CYCLIN D1, MMP-13, OPG, NFATc1, TGF-β and WNT5A in scaphoid non-unions. Interestingly, RANKL and NFATc1, both markers for osteoclastogenesis, were significantly induced in non-unions. Moreover, WNT5A was highly up-regulated in all non-union samples. TRAP staining confirmed the observation of induced osteoclastogenesis in non-unions. With respect to genes related to osteogenesis, alkaline phosphatase was significantly up-regulated 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 increased osteoclast activity in scaphoid non-unions possibly as a result of the alterations in RANKL, TGF-β and WNT5A expression levels. 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 to avoid secondary damages and prevent occurrence of non-unions to scaphoid bones.

【 授权许可】

CC BY   
© 2015 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

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