Anti-inflammatory effect of MAPK phosphatase-1 local gene transfer in inflammatory bone loss

Alveolar bone loss associated with periodontal diseases is the result of osteoclastogenesis induced by bacterial pathogens. The mitogen-activated protein kinase (MAPK) phosphatase 1 (MKP-1) is a critical negative regulator of immune response as a key phosphatase capable of dephosphorylating activated MAPKs. In this study, rat macrophages transduced with recombinant adenovirus (Ad.)MKP-1 specifically dephosphorylated activated MAPKs induced by lipopolysaccharide (LPS) compared with control cells. Bone marrow macrophages from MKP-1 knockout (KO) mice exhibited higher interleukin (IL)-6, IL-10, tumor necrosis factor (TNF)-α, and select chemokine compared with wild-type (WT) mice when stimulated by LPS. In addition, bone marrow cultures from MKP-1 KO mice exhibited significantly more osteoclastogenesis induced by LPS than when compared with WT mice. Importantly, MKP-1 gene transfer in bone marrow cells of MKP-1 KO mice significantly decreased IL-6, IL-10, TNF-α and chemokine levels, and formed fewer osteoclasts induced by LPS than compared with control group of cells. Furthermore, MKP-1 gene transfer in an experimental periodontal disease model attenuated bone resorption induced by LPS. Histological analysis confirmed that periodontal tissues transduced with Ad. MKP-1 exhibited less infiltrated inflammatory cells, less osteoclasts and less IL-6 than compared with rats of control groups. These studies indicate that MKP-1 is a key therapeutic target to control of inflammation-induced bone loss.

Silencing mitogen-activated protein kinase-activated protein kinase-2 arrests inflammatory bone loss

p38 mitogen-activated protein kinases (MAPKs) are critical for innate immune signaling and subsequent cytokine expression in periodontal inflammation and bone destruction. In fact, previous studies show that systemic p38 MAPK inhibitors block periodontal disease progression. However, development of p38 MAPK inhibitors with favorable toxicological profiles is difficult. Here, we report our findings regarding the contribution of the downstream p38 MAPK substrate, mitogen-activated protein kinase-activated protein kinase 2 (MK2 or MAPKAPK-2), in immune response modulation in an experimental model of pathogen-derived lipopolysaccharide (LPS)-induced periodontal bone loss. To determine whether small interfering RNA (siRNA) technology has intraoral applications, we initially validated MK2 siRNA specificity. Then, gingival tissue surrounding maxillary molars of rats was injected with MK2 siRNA or scrambled siRNA at the palatal regions of bone loss. Intraoral tissues treated with MK2 siRNA had significantly less MK2 mRNA expression compared with scrambled siRNA-treated tissues. MK2 siRNA delivery arrested LPS-induced inflammatory bone loss, decreased inflammatory infiltrate, and decreased osteoclastogenesis. This proof-of-concept study suggests a novel target using an intraoral RNA interference strategy to control periodontal inflammation.

The H2S-releasing naproxen derivative, ATB-346, inhibits alveolar bone loss and inflammation in rats with ligature-induced periodontitis

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Mineral Loss and Morphological Changes in Dental Enamel Induced by a 16% Carbamide Peroxide Bleaching Gel

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

P300 in individuals with sensorineural hearing loss

INTRODUCTION: Behavioral and electrophysiological auditory evaluations contribute to the understanding of the auditory system and of the process of intervention. OBJECTIVE: To study P300 in subjects with severe or profound sensorineural hearing loss. METHODS: This was a descriptive cross-sectional prospective study. It included 29 individuals of both genders with severe or profound sensorineural hearing loss without other type of disorders, aged 11 to 42 years; all were assessed by behavioral audiological evaluation and auditory evoked potentials. RESULTS: A recording of the P3 wave was obtained in 17 individuals, with a mean latency of 326.97 ms and mean amplitude of 3.76 V. There were significant differences in latency in relation to age and in amplitude according to degree of hearing loss. There was a statistically significant association of the P300 results with the degrees of hearing loss (p = 0.04), with the predominant auditory communication channels (p < 0.0001), and with time of hearing loss. CONCLUSIONS: P300 can be recorded in individuals with severe and profound congenital sensorineural hearing loss; it may contribute to the understanding of cortical development and is a good predictor of the early intervention outcome.