Cyclic mechanical stretching activates jun n-terminal kinase and modulates apoptosis in human patellar tendon fibroblasts

M. Skutek, M. Van Griensven, J. Zeichen, U. Brauer, N. Bosch

Research output: Contribution to journalArticlepeer-review

Abstract

Objective: To identify the signal transduction pathways in human tendon fibroblasts as a basis for adaptation to physiologcal mechanical stretching in order to optimize tissue engineering in terms of apoptosis. Methods: Human patellar tendon fibroblasts of 5 patients were cultured from remnants of patients undergoing surgical treatment of knee joint instability. Fibroblasts of the 3rd passage were cultured on elastic silicone dishes. Cells were biaxially stretched for 15 or 60 minutes with 1 Hz and an elongation of 5%. Activation of Stress-Activated Protein Kinase/c-Jun NH2-terminal Kinase (SAPK/JNK) was measured using Western blot analysis. Apoptotic cells were determined by annexin-V staining. Results: Application of 15 minutes stretch increased activation of SAPK/JNK after 60 minutes incubation. In concordance, the rate of apoptosis was increased. Interestingly, increased JNK activation was not seen after longer stretch-periods, implicating a rapid inactivation/dephoshorylation. Conclusions: We conclude that the pattern of JNK/SAPK activation and the subsequent temporary apoptotic response represents an acomodation process to the applied mechanical stretching. This novel observation is an important issue for tissue engeneering, as the applied stretching parameters are physiologic and therefore useful for stimulation of cell proliferation and generation of extracellular matrix synthesis.

Original languageEnglish
Pages (from-to)474
Number of pages1
JournalLangenbeck's Archives of Surgery
Volume386
Issue number6
StatePublished - 2001
Externally publishedYes

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