Headquarters, Hospital Authority, Sheung Wan, Hong Kong Special Administrative Region, China.
Rheumatology (Oxford). 2013 Sep;52(9):1609-18. doi: 10.1093/rheumatology/ket214. Epub 2013 Jun 17.
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.
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.
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.
Activation of the Wnt signalling pathway and its effect on TDSCs might contribute to tissue metaplasia and failed healing in some cases of tendinopathy.
在骨化失败的动物模型和肌腱病的临床样本中都观察到组织化生。Wnt 信号通路在病理性钙化中起着至关重要的作用。我们假设 Wnt 信号通路可能导致肌腱病中的组织化生和愈合失败。本研究旨在检查骨化失败的肌腱愈合动物模型和肌腱病的临床样本中 Wnt 途径介质的时空表达。还研究了 Wnt3a 对肌腱源性干细胞（TDSCs）成骨分化的影响。
通过向大鼠髌腱注射胶原酶诱导骨化失败的肌腱愈合。在不同时间点采集肌腱，进行 Wnt3a、β-catenin、Lrp5 和 Tcf1 的免疫组织化学染色。从 13 例髌腱病患者（11 例未骨化和 2 例骨化）和 10 例对照中获得髌腱样本。同样进行了 Wnt3a、β-catenin、Lrp5 和 Tcf1 的免疫组织化学染色。用 Wnt3a 处理大鼠髌腱 TDSCs。通过碱性磷酸酶（ALP）活性、茜素红 S 染色和成骨标志物的 mRNA 表达来检测 TDSCs 的成骨分化。
在动物模型中的愈合成纤维样细胞、软骨样细胞和骨化沉积物以及一些肌腱病的临床样本中，Wnt3a、β-catenin、Lrp5 和 Tcf1 的表达增加。Wnt3a 增加了 TDSCs 的 ALP 活性、钙结节形成和成骨标志物的表达。
Wnt 信号通路的激活及其对 TDSCs 的影响可能导致某些肌腱病中的组织化生和愈合失败。
