Liu Xiangzhou, Chen Wan, Zhou You, Tang Kanglai, Zhang Jiqiang
Department of Orthopaedics, Southwest Hospital, Third Military Medical University, Chongqing, China.
Cell Physiol Biochem. 2015;36(2):517-30. doi: 10.1159/000430117. Epub 2015 May 11.
BACKGROUND/AIMS: Tendinopathy is a common sports injury that is manifested by the heterotopic ossification of tendon tissue. Tendon stem cells (TSCs) are prone to osteogenic differentiation under excessive tension. The underlying mechanisms remain poorly understood.
Uniaxial mechanical tension (UMT) served to stretch rat tendon-derived stem cells (rTDSCs) at 8% elongation (frequency: 1 Hz; 48, 60, or 72 hours).
The osteogenic differentiation of rTDSCs appeared after UMT along with increased mRNA expression of the osteogenic genes Runx2, Dlx5, Alpl, and Col1a1 and increased Runx2 protein expression. Wnt5a, Wnt5b and P-JNK protein levels were also upregulated after UMT stimulation. The inhibition of JNK expression by SP600125 and JNK1-shRNA decreased UMT-induced Runx2 protein expression, and the activation of JNK expression by anisomycin and JNK1-cDNA increased UMT-induced Runx2 protein expression. When shRNA knocked down Wnt5a and Wnt5b expression in rTDSCs, the induction of Runx2 and P-JNK expression by UMT was reduced. The inhibition of Runx2 expression could be rescued by the activation of JNK expression by anisomycin.
UMT induced the osteogenic differentiation of rTDSCs via the Wnt5a/Wnt5b/JNK signaling pathway. Accordingly, this pathway may influence the heterotopic ossification of tendon tissue subjected to excessive tension.
背景/目的：肌腱病是一种常见的运动损伤，表现为肌腱组织的异位骨化。肌腱干细胞（TSCs）在过度张力下易于发生成骨分化。其潜在机制仍知之甚少。
采用单轴机械张力（UMT）以8%的伸长率拉伸大鼠肌腱来源的干细胞（rTDSCs）（频率：1Hz；48、60或72小时）。
UMT后rTDSCs出现成骨分化，同时成骨基因Runx2、Dlx5、Alpl和Col1a1的mRNA表达增加，Runx2蛋白表达增加。UMT刺激后Wnt5a、Wnt5b和P-JNK蛋白水平也上调。SP600125和JNK1-shRNA抑制JNK表达可降低UMT诱导的Runx2蛋白表达，茴香霉素和JNK1-cDNA激活JNK表达可增加UMT诱导的Runx2蛋白表达。当shRNA敲低rTDSCs中Wnt5a和Wnt5b的表达时，UMT对Runx2和P-JNK表达的诱导作用减弱。茴香霉素激活JNK表达可挽救Runx2表达的抑制。
UMT通过Wnt5a/Wnt5b/JNK信号通路诱导rTDSCs的成骨分化。因此，该通路可能影响承受过度张力的肌腱组织的异位骨化。
