Julius Wolff Institute, Charité-Universitaetsmedizin Berlin, Germany.
Berlin-Brandenburg Center for Regenerative Therapies, Charité-Universitaetsmedizin Berlin, Germany.
Sci Rep. 2016 Jul 11;6:29703. doi: 10.1038/srep29703.
The incidence of tendon re-tears post-surgery is an ever present complication. It is suggested that the application of biological factors, such as bone morphogenetic protein 7 (BMP-7), can reduce complication rates by promoting tenogenic characteristics in in vitro studies. However, there remains a dearth of information in regards to the mechanisms of BMP-7 signalling in tenocytes. Using primary human tenocyte-like cells (hTLCs) from the supraspinatus tendon the BMP-7 signalling pathway was investigated: induction of the BMP associated Smad pathway and non-Smad pathways (AKT, p38, ERK1/2 and JNK); alterations in gene expression of BMP-7 associated receptors, Smad pathway components, Smad target gene (ID1) and tenogenic marker scleraxis. BMP-7 increases the expression of specific BMP associated receptors, BMPR-Ib and BMPR-II, and Smad8. Additionally, BMP-7 activates significantly Smad1/5/8 and slightly p38 pathways as indicated by an increase in phosphorylation and proven by inhibition experiments, where p-ERK1/2 and p-JNK pathways remain mainly unresponsive. Furthermore, BMP-7 increases the expression of the Smad target gene ID1, and the tendon specific transcription factor scleraxis. The study shows that tenocyte-like cells undergo primarily Smad8 and p38 signalling after BMP-7 stimulation. The up-regulation of tendon related marker genes and matrix proteins such as Smad8/9, scleraxis and collagen I might lead to positive effects of BMP-7 treatment for rotator cuff repair, without significant induction of osteogenic and chondrogenic markers.
术后肌腱再次撕裂的发生率是一个普遍存在的并发症。有研究表明，应用骨形成蛋白 7（BMP-7）等生物因子可以通过促进体外研究中的腱细胞特性来降低并发症发生率。然而，关于 BMP-7 信号在肌腱细胞中的作用机制仍缺乏信息。本研究使用来源于冈上肌腱的原代人肌腱细胞样细胞（hTLCs），研究了 BMP-7 信号通路：诱导 BMP 相关的 Smad 通路和非 Smad 通路（AKT、p38、ERK1/2 和 JNK）；BMP-7 相关受体、Smad 通路成分、Smad 靶基因（ID1）和腱细胞标志物 Scleraxis 的基因表达变化。BMP-7 增加了特定的 BMP 相关受体 BMPR-Ib 和 BMPR-II 的表达，以及 Smad8 的表达。此外，BMP-7 显著激活了 Smad1/5/8 通路，稍微激活了 p38 通路，这可以通过磷酸化增加来证明，并通过抑制实验证实，其中 p-ERK1/2 和 p-JNK 通路仍然主要无反应。此外，BMP-7 增加了 Smad 靶基因 ID1 和腱特异性转录因子 Scleraxis 的表达。本研究表明，BMP-7 刺激后，肌腱细胞样细胞主要发生 Smad8 和 p38 信号转导。肌腱相关标记基因和基质蛋白（如 Smad8/9、Scleraxis 和 I 型胶原）的上调可能导致 BMP-7 治疗肩袖修复的积极效果，而不会显著诱导成骨和软骨形成标记物。
