Apical periodontitis caused by root canal infection is the most frequent pathological lesion in the jaws, mainly manifested as periapical granulomas and cysts. Understanding of the formation and progression of apical periodontitis as well as the identification of inflammatory biomarkers can help increase the knowledge of pathogenic mechanisms, improve the diagnosis and provide support for different therapeutic strategies. The objective of the present article is to review inflammatory biomarkers such as cytokines, chemokines, inflammatory cells, neuropeptides, RANK/RANKL/OPG system and other inflammatory markers and to relate these systems to the development and progression of pathological conditions related to apical periodontitis.

The influence between dental occlusion and body posture has been discussed in the past ten years by several authors with controversial conclusions. The objective of this study was to access, using surface electromyography (EMG), the rest activity of paired sternocleidomastoids, erectors spinae at L4 level, and soleus muscles in a group of 24 volunteer subjects (12 males, 12 females, aged 23-25 yrs) affected by sub-clinical dental malocclusions in different situations of dental occlusion. The subjects' occlusion was balanced (neuromuscularly) (registered on an acrylic wafer). Rest activity was assessed using the sEMG. The measurements were achieved on subjects while standing barefooted, before (Test 1), and 15 minutes after they wore the acrylic wafer (Test 2). The result was a significant reduction of the mean voltage for each muscle. Paired muscles were registered and the balancing rate between right and left muscles showed improvement for all the paired muscles (Wilcoxon test p < 0.05). No significant difference was noted in the relaxation and balancing rates between the muscles tested. The data confirmed a beneficial effect of balancing the occlusion with an acrylic wafer on the following paired postural muscles: sternocleidomostoid, erector spinae, and soleus.

Occlusal alterations may result in changes in the functional performance of masticatory muscles. In this study, we set up an experimental model in rats to examine whether masticatory muscle abnormalities occur after a malocclusion is induced. Rats underwent unilateral amputation of the molar cusps to simulate an occlusal wear situation. The masseter muscles ipsilateral and contralateral to the amputated molars were excised at different experimental times. Sham-operated rats were used as controls. The tissue samples were studied by light and electron microscopy and morphometry. Tissue calcium content, a biochemical index of muscle injury, was also determined. The results show that occlusal dysfunction leads to microvessel constriction and clear-cut morphologic damage of muscular fibers and blood capillary endothelium, as well as to elevation of tissue calcium content, in the ipsilateral masseter muscle. These changes are likely related to muscle fatigue and ischemia. The early signs of injury do not involve the entire muscle but are mostly restricted to tissue areas rich in type I (slow) muscle fibers, which are characterized by a predominantly aerobic metabolism. The muscle damage becomes more extended and severe with time. On the other hand, the contralateral muscles show only slight alterations which are reversible with time, possibly due to an adaptive response.

In an attempt to verify the nature of bone resorption processes on the bone surrounding radicular cysts, fragments of cysts with the adjacent bone tissue were studied by morphological, cytochemical and ultrastructural methods. Cyst fluid was analysed for its content of cytokines with osteolytic activity. The cyst wall exhibited several connective tissue extensions which penetrated the adjacent bone. Numerous multinucleated tartrate-resistant acid phosphatase (TRAP)-positive cells were seen at the tip of the intraosseous extensions of the cyst capsule and in direct contact with the bone tissue. Typical resorption lacunae were identified on the bone surface by scanning electron microscopy. Moreover, mononuclear TRAP-positive cells were seen within the cyst capsule. High levels of prostaglandin E2 (PGE2) and interleukin-6 (IL-6) were detected in the cyst fluids. In conclusion, active bone resorption may contribute significantly to the growth of these lesions within the jaws.

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Asymptomatic Apical Periodontitis is essentially an inflammatory disease of microbial aetiology. Association and function of the cell components involved, or specific inductive factors and growth mediators associated with development, maintenance and resolution of the periapical lesions are still unknown. The objective of this study was to evaluate the concentration of Regulatory T cells (FoxP3+; Treg), Langerhans cells (CD1a+; LC) and mast cells in asymptomatic apical periodontitis. 73 cases were selected: 30 periapical granulomas, 29 radicular cysts and 14 residual cysts. All groups were submitted to morphological analysis for classification of inflammatory infiltrate and thickness of the epithelial lining as well as to immunohistochemical analysis for detection of LC and Treg cells. Toluidine blue staining was used for detecting mast cells. Analysis showed higher mean numbers of LC (8.2 cells/0.2mm 2), and Treg cells in radicular cysts (5.910 cells/0.2mm 2). As for mast cells, it was found that radicular cysts had a higher mean number of these cells compared to other periapical lesions (12.68 cells/0.2mm 2). The association between thickness of the epithelial lining and inflammatory cells showed that the presence of hypertrophic epithelium in radicular cysts presented higher density of LC. The number of LC and Treg cells play an important role in the control of the inflammatory micro-environment in periapical granulomas and radicular cysts, respectively. The presence of mast cells in radicular cysts may be associated with progression of the lesion. Knowledge regarding the inflammatory cell profile is therefore essential for a better understanding of the pathogenesis of asymptomatic periapical periodontitis.

This study showed that HBO therapy improved early bone regeneration in diabetic rats and increased the mast cell population only in non-diabetic animals. HBO was shown to be important treatment for minimizing deleterious effects of diabetes on bone regeneration.

In previous studies, we showed that the introduction of occlusal alterations to rats results in masseter muscle abnormalities. Here, we investigate whether administration of the muscle relaxant dantrolene to rats with occlusal alteration could counteract the occurrence of such abnormalities. Rats underwent unilateral amputation of molar cusps to cause malocclusion. Some rats received dantrolene (10 mg/kg/day subcutaneously). The masseter muscles ipsilateral to the amputated molars were excised 26 days later. Sham-operated rats were used as controls. The tissue samples were studied by light and electron microscopy and morphometry. Moreover, tissue Ca2+ content, an index of muscle injury, was determined. In the absence of dantrolene, occlusal alteration leads to microvessel constriction, morphologic damage of masseter muscle fibers and blood capillaries, and elevation of tissue Ca2+ content. These changes were nearly abrogated by dantrolene, thus supporting it as a possible new therapeutic tool for the treatment of malocclusion-induced muscle diseases.