title: Oxidative stress-induced c-Jun N-terminal kinase (JNK) activation in tendon cells upregulates MMP1 mRNA and protein expression.
abstract: To explore the potential mechanisms of tendon degeneration, we investigated the role of c-Jun N-terminal Kinase (JNK) activation and the regulation of matrix metalloproteinase 1 (MMP1) in tendon matrix degradation under oxidative stress. JNK and MMP1 activity in samples from normal and ruptured human supraspinatus tendons was evaluated by immunohistochemistry. Real-time quantitative PCR was utilized to evaluate MMP1 mRNA expression and Western blotting for MMP1 and JNK protein detection. JNK activation and increased MMP1 activity were found in the torn human supraspinatus tendon tissue, as well as in human tendon cells under in vitro oxidative stress. Inhibition of JNK prevented MMP1 overexpression in oxidative stressed human tendon cells. Results from the current study indicated that stress activated JNK plays an important role in tendon matrix degradation, possibly through upregulating of MMP1.
authors.affiliation: Orthopaedic Research Institute, St. George Hospital, University of New South Wales, ORI Level 2, 4-10 South Street, Kogarah, NSW 2217, Sydney, Australia.
authors.forename: Fang
authors.initials: F
authors.lastname: Wang
authors.forename: George A C
authors.initials: GA
authors.lastname: Murrell
authors.forename: Min-Xia
authors.initials: MX
authors.lastname: Wang
mesh_terms: D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D066298:In Vitro Techniques; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism*; D020781:Matrix Metalloproteinase 1 / Q000378:metabolism*; D018384:Oxidative Stress / Q000502:physiology*; D012333:RNA, Messenger / Q000378:metabolism; D013710:Tendons / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D012333:RNA, Messenger; D006861:Hydrogen Peroxide; D048031:JNK Mitogen-Activated Protein Kinases; D020781:Matrix Metalloproteinase 1