In this regard the exact

In this regard, the exact molecular and cellular mechanisms responsible for the above observations are not fully understood at this time. In fact, the overall picture suggests that ECM is an important regulator of cell functions, it serves as storage for various growth factors and participates in the regulation of their activation. Thus, altered abundance or composition of ECM may play an active part in the pathogenesis of GO in both DIGO and HGF, characterized by an accumulation of excess ECM and over production of interstitial collagen, glycosaminoglycan and fibronectin by fibroblast. Here the role of TGF-β1 in this process is of interest, because LY335979 cost of TGF-β1 is upregulated in both HGF and DIGO. In both conditions it can promote ECM accumulation by increasing ECM synthesis. It can also inhibit ECM breakdown by down regulating MMP-9 expression, and by increasing expression of TIMP-1 that suppress the activity of MMP-9. It is well known that a high ratio of TIMPs to MMPs results in excess collagen accumulation [43]. Ravanti et al., [44], Leivonen et al., [45] and Ala-aho and Kahari, [46], demonstrated that exogenous or autocrine TGF-β1 upregulates interstitial collagen (type 1 collagen) and down regulates MMP-1 expression in gingival fibroblasts. However, it has been reported that the expression of TIMP-1 and TIMP-2 is down regulated or unaltered in HGF fibroblasts. Thus, it is possible that fibroblasts in HGF, inherently or as a response to elevated TGF- β1 activity, produce less MMPs and more ECM proteins as compared with normal cells, resulting in ECM accumulation. Interestingly, HGF may also involve altered cross-linking of collagen, resulting in increased resistance to degradation [47]. Collagen phagocytosis by fibroblasts is one of the major mechanisms of collagen turnover during tissue maintenance, suggesting that fibrotic lesions, especially in the absence of inflammation, may arise from a reduction in the proportion of fibroblasts that degrade collagen intracellularly [48]. Moreover, the internalization and lysosomal degradation of collagen by cells in HGF is also mediated by an endocytotic process that involves the cell-surface receptor Endo 180, which is expressed by various human gingival cells, including fibroblasts, but its expression and function in HGF have not been studied in detail [49].
Conclusion
Conflict of interest
Introduction The ultimate goal of chemomechanical preparation of infected root canals is complete eradication of intracanal bacteria or their reduction to levels that create a favorable environment for the healing of periradicular tissue [1]. This goal is not always achieved for several reasons, including anatomical complexities and limitations of instruments and medicaments [2–8]. Therefore, alternative strategies have been developed to overcome the limitations of current instrumentation, including alternative instrument design, supplementation of irrigation by sonic or ultrasonic energy, and the use of final MTAD (a mixture of a tetracycline isomer, an acid, and a detergent) or chlorhexidine (CHX) rinses [9]. The self-adjusting file (SAF) has proven superior in terms of disinfection in ex vivo and in vivo models [10–12]. Nevertheless, root canals can still harbor bacteria after SAF instrumentation [10,11]. For enhanced disinfection, a supplementary step is required after chemomechanical preparation. Commonly recommended supplementary approaches include a final rinse with CHX or sonic and ultrasonic irrigation. A final rinse with CHX after chemomechanical preparation has the advantage of the prolonged residual antimicrobial effects provided by CHX [13] and has shown promising results in terms of enhanced root canal disinfection [14,15]. However, in many cases, detectable levels of bacteria persist in the main root canal [16]. Sonic and ultrasonic energy reportedly enhances disinfection through cavitation, acoustic streaming, and sodium hypochlorite (NaOCl) warming, although findings from previous antibacterial studies have been inconclusive [14,17–20].