title: Human scaphoid non-unions exhibit increased osteoclast activity compared to adjacent cancellous bone.
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.
authors.affiliation: Department of Plastic Surgery, BG University Hospital Bergmannsheil, Ruhr University Bochum, Bochum, Germany.
authors.forename: Jessica
authors.initials: J
authors.lastname: Schira
authors.affiliation: Department of Plastic Surgery, BG Trauma Hospital Ludwigshafen, University of Heidelberg, Ludwigshafen, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Schulte
authors.affiliation: Department of Plastic Surgery, BG Trauma Hospital Ludwigshafen, University of Heidelberg, Ludwigshafen, Germany.
authors.forename: Carmen
authors.initials: C
authors.lastname: Döbele
authors.affiliation: Department of Plastic Surgery, BG University Hospital Bergmannsheil, Ruhr University Bochum, Bochum, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Wallner
authors.affiliation: Department of Plastic Surgery, BG University Hospital Bergmannsheil, Ruhr University Bochum, Bochum, Germany.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Abraham
authors.affiliation: Department of Plastic Surgery, BG University Hospital Bergmannsheil, Ruhr University Bochum, Bochum, Germany.
authors.forename: Adrien
authors.initials: A
authors.lastname: Daigeler
authors.affiliation: Department of Plastic Surgery, BG Trauma Hospital Ludwigshafen, University of Heidelberg, Ludwigshafen, Germany.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Kneser
authors.affiliation: Department of Plastic Surgery, BG University Hospital Bergmannsheil, Ruhr University Bochum, Bochum, Germany.
authors.forename: Marcus
authors.initials: M
authors.lastname: Lehnhardt
authors.affiliation: Department of Plastic Surgery, BG University Hospital Bergmannsheil, Ruhr University Bochum, Bochum, Germany.
authors.forename: Björn
authors.initials: B
authors.lastname: Behr
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001842:Bone and Bones / Q000293:injuries / Q000378:metabolism*; D005260:Female; D050723:Fractures, Bone / Q000235:genetics* / Q000378:metabolism; D020869:Gene Expression Profiling / Q000379:methods*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D008957:Models, Genetic; D010010:Osteoclasts / Q000378:metabolism*; D010012:Osteogenesis / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000235:genetics; D055815:Young Adult
keywords: RANKL; WNT5A; non-union; osteoclasts; scaphoid