Regulated factors of NF-kB activity in synovial fibroblasts by repetitive mechanical stretch

• Project/Area Number: 17592095
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Surgical dentistry
• Research Institution: Nara Medical University
• Principal Investigator: KAWAKAMI Tetsuji Nara Medical University, Oral and Maxillofacial Surgery, Assistant professor, 医学部, 講師 (60254512)
• Co-Investigator(Kenkyū-buntansha): TANAKA Yasuharu Nara Medical University, Biochemistry, Associate Professor, 医学部, 助教授 (20124878)
• Project Period (FY): 2005 – 2006
• Project Status: Completed (Fiscal Year 2006)
• Budget Amount: ¥3,500,000 (Direct Cost: ¥3,500,000); Fiscal Year 2006: ¥1,000,000 (Direct Cost: ¥1,000,000); Fiscal Year 2005: ¥2,500,000 (Direct Cost: ¥2,500,000)
• Keywords: Temporomandibular joint (TMJ) / Cyclooxygenase-2 (COX-2) / Mechanical stretch / Svnovial fibroblasts / Nuclear factor-κB (NF-κB) / 培養滑膜細胞(HIG-82) / Nuclear factorκB (NF-κB) / Nuclear factor κB(NF-κB)

Research Abstract

It is proposed that synovial inflammation mediated by induced cyclooxygenase-2 (COX-2) has important roles in the onset of temporomandibular joint (TMJ) pain. However, we have little knowledge about the pathophysiology of TMJ pain. In our previous studies, we have demonstrated that COX-2 and the transcription factor nuclear factor κB (NF-κB) were induced in lapine synovial fibroblast cells (HIG-82) by excessive mechanical stretch (140% peak to peak). In this study, we examined whether COX-2 and NF-κB were induced in HIG-82 cells by repetitive and weak stretch (120% peak to peak) such as bruxism and clenching. Moreover, we examined regulated factors of NF-κB activity induced by mechanical stretch in HIG-82 cells.
Reporter gene assay showed that NF-κB activity in HIG-82 transiently increased according to the increase of stretching periods and decreased gradually, suggesting that NF-κB activity in HIG-82 with dynamic weak repetitive stretch was significantly higher than static excessive st retch. Similarly, COX-2 protein induced by repetitive mechanical stress transiently increased. This suggested that synovial inflammation due to repetitive motion might lead to TMJ pain.
To examine regulated factors of NF-κB activity induced by mechanical stretch in HIG-82 cells, the cells were incubated for 1 hour with some COX-2 inhibitors (BAY11-7085 (2μM), curcumin (10〜40μM), MG132 (2μM), PDTC (5μM), and SP600125 (5μM) ) prior to cycling stretch. NF-κB activity in response to stretching is significantly suppressed by COX-2 inhibitor (curcumin, BAY11-7085, MG132 and PDTC). Similarly, COX-2 inhibitors suppressed induction of COX-2 in response to repetitive stretch. Among them, curcumin, a major component of food spice turmeric, is known for anti-inflammatory and antioxidant properties. This suggested that pharmacotherapy using COX-2 inhibitors (e.g. curcumin) could be applied to a new treatment for TMD.
The present study suggested that synovial inflammation due to repetitive motion, such as bruxism and clenching, might lead to TMJ pain, and that inflammation of synoviocyte was able to suppress by pretreatment of COX-2 inhibitors.