title: Expression of Wnt pathway mediators in metaplasic tissue in animal model and clinical samples of tendinopathy.
abstract: OBJECTIVE
  Tissue metaplasia is observed in both ossified failed healing animal model and clinical samples of tendinopathy. The Wnt signalling pathway plays a vital role in pathological calcification. We hypothesized that the Wnt signalling pathway might contribute to tissue metaplasia and failed healing in tendinopathy. This study aimed to examine the spatial-temporal expression of Wnt pathway mediators in an ossified failed tendon healing animal model and clinical samples of tendinopathy. The effect of Wnt3a on the osteogenic differentiation of tendon-derived stem cells (TDSCs) was also examined.
  
  
  METHODS
  Ossified failed tendon healing was induced by the injection of collagenase into the patellar tendon of rats. At various times the tendons were harvested for immunohistochemical staining of Wnt3a, β-catenin, Lrp5 and Tcf1. Patellar tendon samples were obtained from 13 patients with patellar tendinopathy (11 unossified and 2 ossified) and 10 controls. Immunohistochemical staining of Wnt3a, β-catenin, Lrp5 and Tcf1 was similarly performed. Rat patellar TDSCs were treated with Wnt3a. The osteogenic differentiation of TDSCs was examined by ALP activity, alizarin red S staining and mRNA expression of osteogenic markers.
  
  
  RESULTS
  There was increased expression of Wnt3a, β-catenin, Lrp5 and Tcf1 in the healing fibroblast-like cells, chondrocyte-like cells and ossified deposits in the animal model and in some clinical samples of tendinopathy. Wnt3a increased ALP activity, calcium nodule formation and expression of osteogenic markers in TDSCs.
  
  
  CONCLUSIONS
  Activation of the Wnt signalling pathway and its effect on TDSCs might contribute to tissue metaplasia and failed healing in some cases of tendinopathy.
authors.affiliation: Headquarters, Hospital Authority, Sheung Wan, Hong Kong Special Administrative Region, China. paulinelui00@gmail.com
authors.forename: Pauline Po Yee
authors.initials: PP
authors.lastname: Lui
authors.forename: Yuk Wa
authors.initials: YW
authors.lastname: Lee
authors.forename: Yin Mei
authors.initials: YM
authors.lastname: Wong
authors.forename: Xiaoling
authors.initials: X
authors.lastname: Zhang
authors.forename: Kerong
authors.initials: K
authors.lastname: Dai
authors.forename: Christer Gustav
authors.initials: CG
authors.lastname: Rolf
mesh_terms: D000328:Adult; D000818:Animals; D002114:Calcinosis / Q000378:metabolism* / Q000473:pathology; D019902:Chondrocytes / Q000378:metabolism / Q000473:pathology; D005260:Female; D051538:Hepatocyte Nuclear Factor 1-alpha / Q000378:metabolism; D006801:Humans; D060492:Low Density Lipoprotein Receptor-Related Protein-5 / Q000378:metabolism; D008297:Male; D008679:Metaplasia / Q000378:metabolism / Q000473:pathology; D010012:Osteogenesis / Q000502:physiology*; D017847:Patellar Ligament / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013234:Stem Cells / Q000378:metabolism / Q000473:pathology; D052256:Tendinopathy / Q000378:metabolism* / Q000473:pathology; D060449:Wnt Signaling Pathway / Q000502:physiology*; D060509:Wnt3A Protein / Q000378:metabolism; D051176:beta Catenin / Q000378:metabolism
chemical_list: C496487:HNF1A protein, human; D051538:Hepatocyte Nuclear Factor 1-alpha; C555482:LRP5 protein, human; D060492:Low Density Lipoprotein Receptor-Related Protein-5; D060509:Wnt3A Protein; D051176:beta Catenin
keywords: Wnt signalling; metaplasia; ossification; tendinopathy; tendon stem/progenitor cells; tendon-derived stem cells (TDSC)