title: Mechanical Tension Promotes the Osteogenic Differentiation of Rat Tendon-derived Stem Cells Through the Wnt5a/Wnt5b/JNK Signaling Pathway.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  Uniaxial mechanical tension (UMT) served to stretch rat tendon-derived stem cells (rTDSCs) at 8% elongation (frequency: 1 Hz; 48, 60, or 72 hours).
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Orthopaedics, Southwest Hospital, Third Military Medical University, Chongqing, China.
authors.forename: Xiangzhou
authors.initials: X
authors.lastname: Liu
authors.forename: Wan
authors.initials: W
authors.lastname: Chen
authors.forename: You
authors.initials: Y
authors.lastname: Zhou
authors.forename: Kanglai
authors.initials: K
authors.lastname: Tang
authors.forename: Jiqiang
authors.initials: J
authors.lastname: Zhang
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D002478:Cells, Cultured; D020935:MAP Kinase Signaling System; D008297:Male; D010012:Osteogenesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism; D013314:Stress, Mechanical; D013710:Tendons / Q000166:cytology*; D051153:Wnt Proteins / Q000378:metabolism*
chemical_list: D051153:Wnt Proteins; C502524:Wnt5b protein, rat