Recently, Sirtuin 1 (SIRT1) has been implicated in the molecular control of ageing and immune response. Although the remodelling of periodontal ligament (PDL) in response to mechanical stress (MS) is mediated by several host factors, including cytokines and chemokines, the transmission of mechanical stimuli into specific cellular activity is still not understood fully. This study aimed to investigate the effects of MS, particularly cyclic strain, on immune response genes, as well as SIRT1 and its signal transduction pathways, in human PDL cells. MS up-regulated the expression of SIRT1 and immune response genes encoding cytokines [tumour necrosis factor (TNF)-α, interleukin (IL)-1β], chemokines [IL-8, monocyte cheoattractant protein (CCL)-20], defensins [human β-defensin (hBD)-2, hBD-3] and Toll-like receptors (TLR-2 and TLR-4) in a force- and time-dependent manner. The SIRT1 inducers resveratrol and isonicotinamide attenuated MS-induced cytokine and chemokine expression, but enhanced the expression of defensins and TLRs. Blockade of SIRT1 activity by the SIRT1 inhibitors sirtinol and nicotinamide and down-regulation of SIRT1 expression by SIRT1 siRNA reduced the stimulatory effects of MS on defensins and TLRs, but increased its effects on cytokines and chemokines. MS induced activation of protein kinase B (Akt), protein kinase C (PKC), nuclear factor (NF)-κB and p38 mitogen-activated protein kinase (MAPK), c-Jun N-terminal kinase (JNK) and extracellular signal-regulated kinase (ERK). Treatment with the anti-oxidants N-acetylcysteine and glutathione inhibited MS-induced reactive oxygen species production and expression of cytokines, chemokines, defensins and TLRs. These results suggest that MS activates human PDL cells to express immune/defence genes encoding cytokines, chemokines, defensins and TLRs via a SIRT1 pathway.

This study examined the role of focal adhesion kinase (FAK) as a mechanoreceptor in human periodontal ligament (hPDL) cells. hPDL cells were obtained from premolars extracted for orthodontic purposes. Mechanical stress was applied in a compressive manner (2 g/cm²) for various time durations (0.5, 2, 6, 24, 48 hrs) with or without a knockdown treatment for FAK. Compressive stimulation increased the level of phosphorylated FAK and prostaglandin E₂ production. The FAK-knockdown cells showed significantly lower prostaglandin E₂ levels than the control cells. Furthermore, compressive stress up-regulated cyclo-oxygenase-2 mRNA, whereas there were no changes observed in the FAK-knockdown cells. These results suggest that FAK regulates the production of prostaglandin E₂ via the transcriptional regulation of COX-2 mRNA in compressive stimulated PDL cells. The FAK-integrin complex plays a role in mechanoreception and mechanotransduction in hPDL cells.

Objective: To examine the stability of mini-screws that invade a dental root by measuring the retention period/failure rate, and to illustrate their effects on paradental tissues. Materials and Methods: Three adult male beagle dogs received 48 orthodontic mini-screws. Half of the mini-screws were implanted to invade the roots, and the rest were placed in the middle of the alveolar bone. Half of the mini-screws were loaded immediately. The retention period of the mini-screws was documented. The dogs were euthanized after 8 weeks, and tissue samples were examined histologically. Results: The failure rate of the mini-screws that invaded the roots was 79.2%, and that of the mini-screws in the middle of the alveolar bone was 8.3%. The application of force had little effect on the failed mini-screws. Moderately injured roots were repaired with osteoid and/or cementoid tissues with normal periodontal ligaments, followed by recovery of the original configuration. Conclusion: Orthodontic mini-screws had a higher failure rate when placed to invade the dental roots. However, minimally damaged dental roots do not adversely affect the healing process. (Angle Orthod. 2009:79; )