title: Regulation of plasminogen activator activity and expression by cyclic mechanical stress in rat mandibular condylar chondrocytes.
abstract: To investigate the mechanism of cartilage degradation induced by overloading in the temporomandibular joint (TMJ), the effect of cyclic mechanical compressive stress on the activity of plasminogen activator (PA) and the expression of the predominant components of the PA system were analyzed in cultured mandibular condylar chondrocytes (MCCs) in rats. MCCs were exposed to cyclic mechanical compressive stress (2000, 4000 and 6000 µ strain) at 0.5 Hz by a four‑point bending system. The activity of PA was determined by hydrolysis of the chromogenic substrate H‑D-Val-Leu-Lys‑pNA (S‑2251). The mRNA and protein expression levels of urokinase‑type PA (uPA), tissue‑type PA (tPA), uPA receptor (uPAR) and PA inhibitor 1 (PAI‑1) were detected by qPCR and western blot analysis, respectively. Cyclic mechanical stress at 4000 and 6000 µ strain induced the expression of uPA, tPA and uPAR, and increased the activity of PA. Furthermore, cyclic mechanical stress at 6000 µ strain also inhibited the expression of PAI‑1. Analysis of pericellular proteolytic activity demonstrated that PA functioned as the active enzyme in excessive mechanical stress responsiveness (e.g., 4000 and 6000 µ strain) largely via uPAR, not PAI‑1. Cyclic mechanical stress at 2000 µ strain induced the expression of tPA and PAI‑1; however, it did not change the activity of PA. These results suggested that the mechanical induction of uPA, tPA and uPAR upregulated PA activity, which may provide a proteolytic environment of extracellular matrix components and subsequently contribute to the cartilage degradation in TMJ osteoarthritis.
authors: State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan 610041, P.R. China.
authors: Wei
authors: W
authors: Chen
authors: Yaling
authors: Y
authors: Tang
authors: Min
authors: M
authors: Zheng
authors: Jian
authors: J
authors: Jiang
authors: Guiquan
authors: G
authors: Zhu
authors: Xinhua
authors: X
authors: Liang
authors: Mingzhe
authors: M
authors: Li
mesh_terms: D000818:Animals; D001696:Biomechanical Phenomena; D002478:Cells, Cultured; D019902:Chondrocytes / Q000502:physiology*; D015870:Gene Expression; D005786:Gene Expression Regulation; D008335:Mandibular Condyle / Q000166:cytology*; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D055293:Receptors, Urokinase Plasminogen Activator / Q000235:genetics / Q000378:metabolism*; D013312:Stress, Physiological; D010959:Tissue Plasminogen Activator / Q000235:genetics / Q000378:metabolism*; D014568:Urokinase-Type Plasminogen Activator / Q000235:genetics / Q000378:metabolism*
chemical_list: D017395:Plasminogen Activator Inhibitor 1; D012333:RNA, Messenger; D055293:Receptors, Urokinase Plasminogen Activator; D010959:Tissue Plasminogen Activator; D014568:Urokinase-Type Plasminogen Activator