Graphs depicting the bone volume.

<p>(A) Condyle, (B) Attachment of the masseter, (C) The part below the second tooth. **Significant difference between both groups (p<0.05).</p

Graphs depicting the BV/TV.

<p>(A) Condyle, (B) Attachment of the masseter, (C) The part below the second tooth. **Significant difference between both groups (p<0.05).</p

Additional file 1: Table S1. of Production of infectious HCV genotype 1b virus in cell culture using a novel Set of adaptive mutations

List of Primers. (PDF 34 kb

Landmarks and measurement items for linear analysis (A) and angular analysis (B) by 3D reconstructions.

<p>Me: Menton (most inferior point of mandibular symphysis). Gn: Gnathion (most anterior point on bony contour of mandibular symphysis). Go: Gonion (most outward and everted point on angle formed by junction of ramus and body of mandible). Co: Condylion (most superoposterior point on mandibular condyle). Cp: Coronoid process (most superior point on coronoid process of mandible). Me-Co: Total length of the mandible (distance measured between menton and condylion). Me-Go: Base length of the mandible (distance measured between menton and gonion). CpH: Height of coronoid process (a perpendicular line from coronoid process to the line connected to gnathion and menton). CoH: Height of mandibular ramus (a perpendicular line from condylion to the line connected to gnathion and menton). CoGo/GnMe: Gonial angle (angle made from the line connected to condylion and gonion and the line connected to gnathion and menton). CoGn/GnMe: Ramus angle (angle made from condylion, gnathion and menton).</p

Graphs depicting the material mineralization of the cortex at the (A) Condyle, (B) Attachment of the masseter, (C) The part below the second tooth.

<p>**Significant difference between both groups (p<0.05).</p

Lateral (3-A) and medial (3-B) views of the cortical mineralization.

<p>Left column: bones of the hard-diet group, Right column: bones of the soft-diet group. The colours red, yellow, green, blue, and purple indicate mineralization ranges 718.4–863.0, 863.0–1007.7, 1007.7–1152.4, 1152.4–1297.0, and 1297.0–1441.7 mg HA/ccm, respectively.</p

Comparison of mandibular measurements between the hard- and soft-diet groups.

<p>Comparison of mandibular measurements between the hard- and soft-diet groups.</p

A representative 3D reconstructions of the hard-diet group (A) and the soft-diet group (B).

<p>Scale bar = 5 mm. Note the much smaller size of the soft-diet mandible.</p

Rebamipide Attenuates Mandibular Condylar Degeneration in a Murine Model of TMJ-OA by Mediating a Chondroprotective Effect and by Downregulating RANKL-Mediated Osteoclastogenesis

<div><p>Temporomandibular joint osteoarthritis (TMJ-OA) is characterized by progressive degradation of cartilage and changes in subchondral bone. It is also one of the most serious subgroups of temporomandibular disorders. Rebamipide is a gastroprotective agent that is currently used for the treatment of gastritis and gastric ulcers. It scavenges reactive oxygen radicals and has exhibited anti-inflammatory potential. The aim of this study was to investigate the impact of rebamipide both <i>in vivo</i> and <i>in vitro</i> on the development of cartilage degeneration and osteoclast activity in an experimental murine model of TMJ-OA, and to explore its mode of action. Oral administration of rebamipide (0.6 mg/kg and 6 mg/kg) was initiated 24 h after TMJ-OA was induced, and was maintained daily for four weeks. Rebamipide treatment was found to attenuate cartilage degeneration, to reduce the number of apoptotic cells, and to decrease the expression levels of matrix metalloproteinase-13 (MMP-13) and inducible nitric oxide synthase (iNOS) in TMJ-OA cartilage in a dose-dependent manner. Rebamipide also suppressed the activation of transcription factors (e.g., NF-κB, NFATc1) and mitogen-activated protein kinases (MAPK) by receptor activator of nuclear factor kappa-B ligand (RANKL) to inhibit the differentiation of osteoclastic precursors, and disrupted the formation of actin rings in mature osteoclasts. Together, these results demonstrate the inhibitory effects of rebamipide on cartilage degradation in experimentally induced TMJ-OA. Furthermore, suppression of oxidative damage, restoration of extracellular matrix homeostasis of articular chondrocytes, and reduced subchondral bone loss as a result of blocked osteoclast activation suggest that rebamipide is a potential therapeutic strategy for TMJ-OA.</p></div

Effects of rebamipide on apoptosis, MMP-13, and iNOS for the mandibular chondrocyte cells in the mouse model of TMJ-OA.

<p>A, Representative tissue sections from the mandibular condyle of the three experimental groups of TMJ-OA mice (control, vehicle-treated, and R-6; n = 5 mice/group) that underwent TUNEL staining. The number of TUNEL-positive cells (stained brown) for the vehicle-treated, R-0.6, and R-6 tissues were determined, and the data are presented as the mean ± SD. The number of TUNEL-positive cells was significantly attenuated in the condylar cartilage tissues of the R-6 mice compared with the vehicle-treated mice. **<i>P</i> < 0.01. Scale bar = 100 μm. B, C, Serial sections of condylar cartilage from the vehicle-treated and R-6 tissues stained in A were immunostained for cleaved caspase-3 (B) and MMP-13 (C). Expression of both targets were dramatically attenuated in the condylar cartilage of the R-6 mice compared with the vehicle-treated mice. **<i>P</i> < 0.01. Scale bar = 100 μm. D, ATDC5 cells were treated with various concentrations of rebamipide for 48 h, and cell viability was measured in WST-8 assays. E, ATDC5 cells were cultured with or without IL-1β in the absence or presence of rebamipide (Reba) at various concentrations as indicated for 48 h following an initial 24 h of serum starvation. The levels of <i>MMP-13</i> mRNA were measured by quantitative real-time PCR. Detection of <i>GAPDH</i> was used as an internal control. Ct cycles of <i>MMP-13</i> were in the range of 22.0–26.0. Ct cycles of <i>GAPDH</i> were in the range of 15.0–15.7. The data presented are the mean ± SD for three independent experiments that were performed per group. *<i>P</i> < 0.05; **<i>P</i> < 0.01. F, Serial sections of condylar cartilage tissues from vehicle-treated and R-6 mice were immunolabeled for iNOS expression. A lower number of iNOS-positive cells were observed in R-6 than in vehicle-treated tissues. **<i>P</i> < 0.01. Scale bar = 100 μm. As a negative control, mandibular articular cartilage obtained from R-6 mice were stained with rabbit IgG (isotype control).</p