Stromal cell-derived factor-1 regulates the secretion of interleukin-1ß in the temporomandibular joint of rats with synovial inflammation.

BACKGROUND: Synovitis is characterized by the infiltration of inflammatory cells and often accompanies the pathological progression of the clinical symptoms affecting the temporomandibular joint (TMJ), such as pain, snapping, and limited mouth opening. It has been suggested that the signal transduction pathway and resultant proinflammatory mediators play important roles in the pathogenesis of synovitis. Therefore, in this present research, we aimed to investigate the changes in the expressions of stromal cell-derived factor 1 (SDF-1) and interleukin (IL)-1ß in rats with occlusal interference. MATERIALS AND METHODS: We divided 36 male Wistar rats into the following groups: Group A (control group), Group B (occlusal interference group), and Group C (AMD3100 group). Synovial inflammation was induced in the rats in Groups B and C to establish the occlusal interference model. The inflammatory changes were detected, and the expressions of SDF-1 and IL-1ß in the synovium were assayed via immunostaining and a real-time quantitative polymerase chain reaction (PCR). RESULTS: In Group B, obvious inflammatory changes were observed in the synovial membranes; additionally, the SDF-1 and IL-1ß expression levels were significantly higher at the protein and mRNA levels. However, in Group C, these experimental results were inhibited by an injection with AMD3100. CONCLUSION: These results may indicate that SDF-1 regulates the expression level of inflammatory factors, such as IL-1ß, in the synovial membranes of rats with occlusal interference. Our findings suggest that the SDF-1 axis may contribute to the onset of synovitis during the development of TMJ joint disease.

Effect of Toll-Like Receptor 4 on Synovial Injury of Temporomandibular Joint in Rats Caused by Occlusal Interference.

Synovitis is an important disease that causes intractable pain in TMJ. Some investigations suggested that the increasing expression of IL-1ß secreted by synovial lining cells plays an important role in synovial inflammation and cartilage destruction in TMJ. In our previous research, the results demonstrated that TLR4 is involved in the expression of IL-1ß in SFs from TMJ with lipopolysaccharide stimulation. However, the inflammatory response that occurred in synovial membrane is not caused by bacterial infection. In the current study, we investigated whether or not TLR4 participates in the inflammatory responses and the expression of IL-1ß in synovial membrane of rats induced by occlusal interference. The results showed that obvious inflammation changes were observed in the synovial membranes and the expression of TLR4 and IL-1ß was increased at both mRNA and protein levels in the occlusal interference rats. In addition, the inflammation reactions and the increased expression of IL-1ß could be restrained by treatment with TAK-242, a blocker of TLR4 signaling. The results prompted us that the activation of TLR4 may be involved in the inflammatory reactions and increased expression of IL-1ß in patients with synovitis and participate in the mechanisms of the initiation and development of synovial injury by regulating the expression of inflammatory mediators like IL-1ß in synovial membranes.

Effects of HMGB1/TLR4 on secretion IL-10 and VEGF in human jaw bone-marrow mesenchymal stem cells.

OBJECTIVE: We aimed to investigate the regulatory effects of HMGB1/TLR4 signaling pathway on the expression of IL-10 and VEGF in human bone marrow mesenchymal stem cells. METHODOLOGY: Human JBMSCs were isolated and cultured. Then, HMGB1 was added into the JBMSCs culture medium, and the protein and mRNA expression levels of IL-10 and VEGF were assessed. Moreover, cells were pretreated with a specific TLR4 inhibitor (TAK-242), and the expression changes of IL-10 and VEGF were compared. RESULTS: Compared with the control group, exposure to HMGB1 in human JBMSCs up-regulated TLR4, IL-10, and VEGF secretion at both protein and mRNA levels (P<0. 05). In addition, the increased expression of IL-10 and VEGF could be restrained in TAK-242 group compared with the HMGB1 group (P<0.05). CONCLUSIONS: The results indicated that HMGB1 activate TLR4 signaling pathway in Human JBMSCs, which plays a regulatory role in cytokines expression.

Progress in Data Acquisition of Wearable Sensors.

Wearable sensors have demonstrated wide applications from medical treatment, health monitoring to real-time tracking, human-machine interface, smart home, and motion capture because of the capability of in situ and online monitoring. Data acquisition is extremely important for wearable sensors, including modules of probes, signal conditioning, and analog-to-digital conversion. However, signal conditioning, analog-to-digital conversion, and data transmission have received less attention than probes, especially flexible sensing materials, in research on wearable sensors. Here, as a supplement, this paper systematically reviews the recent progress of characteristics, applications, and optimizations of transistor amplifiers and typical filters in signal conditioning, and mainstream analog-to-digital conversion strategies. Moreover, possible research directions on the data acquisition of wearable sensors are discussed at the end of the paper.

Effects of HMGB1/TLR4 on secretion IL-10 and VEGF in human jaw bone-marrow mesenchymal stem cells

Abstract Objective: We aimed to investigate the regulatory effects of HMGB1/TLR4 signaling pathway on the expression of IL-10 and VEGF in human bone marrow mesenchymal stem cells. Methodology: Human JBMSCs were isolated and cultured. Then, HMGB1 was added into the JBMSCs culture medium, and the protein and mRNA expression levels of IL-10 and VEGF were assessed. Moreover, cells were pretreated with a specific TLR4 inhibitor (TAK-242), and the expression changes of IL-10 and VEGF were compared. Results: Compared with the control group, exposure to HMGB1 in human JBMSCs up-regulated TLR4, IL-10, and VEGF secretion at both protein and mRNA levels (P<0. 05). In addition, the increased expression of IL-10 and VEGF could be restrained in TAK-242 group compared with the HMGB1 group (P<0.05). Conclusions: The results indicated that HMGB1 activate TLR4 signaling pathway in Human JBMSCs, which plays a regulatory role in cytokines expression.

Association of occlusal interference-induced masseter muscle hyperalgesia and P2X3 receptors in the trigeminal subnucleus caudalis and midbrain periaqueductal gray.

P2X3 receptor plays a role in nociception transmission of orofacial pain in temporomandibular disorder patients. A previous study found that P2X3 receptors in masseter muscle afferent neurons and the trigeminal ganglia were involved in masseter muscle pain induced by inflammation caused by chemical agents or eccentric muscle contraction. In this study, we attempted to investigate changes in P2X3 receptors in the trigeminal subnucleus caudalis (Vc) and midbrain periaqueductal gray (PAG) in relation to the hyperalgesia of masseter muscles induced by occlusal interference. Experimental occlusal interference by crown application was established in 30 rats and another 30 rats were treated as sham controls. On days 1, 3, 7, 14, and 28 after crown application, the mechanical pain threshold was examined by von-Frey filaments. The expression of the P2X3 receptor in Vc and PAG was investigated by immunohistochemistry and quantitative PCR. We found that mechanical pain threshold of bilateral masseter muscles decreased significantly after occlusal interference, which remained for the entire experimental period. The mRNA expression of the P2X3 receptor increased significantly and the number of P2X3R-positive neurons increased markedly in Vc and PAG accordingly. These results indicate that the upregulated expression of P2X3 receptors in Vc and PAG may contribute toward the development of orofacial pain induced by occlusal interference and P2X3 receptors in the PAG may play a key role in the supraspinal antiociception effect.

Upregulation of the Purinergic Receptor Subtype P2X3 in the Trigeminal Ganglion Is Involved in Orofacial Pain Induced by Occlusal Interference in Rats.

AIMS: To evaluate whether the purinergic receptor subtype P2X3 (P2X3R) in trigeminal ganglion (TG) neurons is involved in hyperalgesia of the temporomandibular joints (TMJs) and masseter muscles associated with placement of an occlusal interference. METHODS: Forty-five rats were randomized into five groups (ie, for days 1, 3, 7, 14, or 28; nine rats per group). Six rats from each group were chosen to receive the occlusal interference, and the remaining three rats were sham-treated controls. On days 1, 3, 7, 14, and 28 after placement of the occlusal interference, the mechanical pain threshold (MPT) to stimulation of the TMJs or masseter muscles was examined using von Frey filaments. Seven days after the occlusal interference placement, changes in MPT were tested after administration of the P2X3R antagonist A-317491 into the TMJs and masseter muscles (60 µg/site) in six rats. The expression of P2X3R in the TGs was investigated by immunohistochemistry and quantitative polymerase chain reaction (qPCR). Retrograde tracing was combined with immunofluorescence to identify TMJ and masseter muscle afferent neurons in the TGs of six premature rats. RESULTS: The TMJ and masseter muscle MPTs were decreased after placement of the occlusal interference, and the P2X3R antagonist reversed the mechanical hyperalgesia that was caused by the occlusal interference placement. The frequency of P2X3R-immunoreactive cells increased in small-sized neurons in the TG after occlusal interference. By contrast, there was no increase in medium-sized TG neurons. P2X3R mRNA increased on day 3. Retrograde tracing indicated that the TMJ and masseter muscle afferent neurons in the TG expressed P2X3R. CONCLUSION: Upregulated P2X3R expression in the TG may contribute to orofacial pain development induced by an occlusal interference. P2X3R may be a therapeutic target for chronic TMJ or masseter muscle pain.

The trophic effect of ciliary neurotrophic factor on injured masseter muscle in rat.

OBJECTIVES: Occlusal trauma is one of the most common forms of oral biting dysfunction. Long-term occlusal trauma could weaken the stomatognathic system; especially damage one's masticatory muscle. Through using the rat model, this study investigated the trophic effect of ciliary neurotrophic factor (CNTF) on injured masseter muscle. MATERIALS AND METHODS: Male Wistar rats (n=36) were randomly divided into five experimental groups and one control group (6 rats per group). Animals in the experimental group were cemented modified crowns on their mandibular first molars to artificially induce occlusal trauma in 1, 3, 7, 14, and 28 days. Control group was sham-treated with forced mouth-opening for about 5 min, while no crowns were placed. After 28 days of treatment, all rats were euthanized and their masseter muscle was collected. Through immunofluorescence and real-time quantitative PCR, the expression of desmin, CNTF, and CNTFRα was investigated in rat masseter muscle. The microstructure of masseter muscle was observed by transmission electron microscope. RESULTS: The expression of desmin showed a time-dependent decrease on traumatic and non-traumatic sides masseter, until reached the nadir at the 14(th) day, then restored to its normal level at the 28(th) day; however, the expression of CNTF and CNTFRα on the traumatic and non-traumatic sides increased from day 7, reached the peak at the 14(th) day, and returned to normal level on the 28(th) day. CONCLUSION: CNTF, as an important neurotrophic factor, was tightly associated to the restoring of rat injured masseter muscle, which provides new target and treatment method for clinical application.

[Studies on the correlation between the expression of Toll-like receptor 4 and the synovitis of the temporomandibular joint in rats].

OBJECTIVE: To investigate the expression of the Toll-like receptor-4 (TLR-4) in temporo-mandibular joint synovitis in rats, and to discuss the correlation between the expression of TLR-4 and the synovitis. METHODS: Sixty male wistar rats were randomly divided into five groups, 12 each. Group A was the control group in which the rats were given normal diet.In Group B, the rats' bilateral masseter muscles were cut off (masseter resection group). In Group C, An cast metal crown were bonded on the mandibular right first molar of each rat (occlusal interference group). In Group D, occlusal pad were bonded on maxillary molars of each rat (occlusal dimension increase group). In Group E, rats' bilateral masseter muscles were re-sected and occlusal pads were bonded on their maxillary molars (masseter resection and occlusal dimension increase group). Pathological changes of synovium were observed using hematoxylin and eosin (HE) stains and pathology scores were evaluated. The expression of TLR- 4 were determined by immunohistochemical stains, and the expression of TLR-4 mRNA were determined by real-time PCR. The correlation between the expression of TLR-4, TLR-4 mRNA and the pathological score were analyzed using Spearman analysis. RESULTS: The pathological scores of Group A-E were 0.5 ± 0.5, 2.5 ± 1.0, 2.7 ± 1.0, 3.0 ± 0.9, 5.3 ± 1.2 respectively. The expression of TLR-4 were (3.2 ± 1.5)%, (16.± 2.6)%, (15.8 ± 2.1)%, (17.5 ± 2.4)%, (38.2 ± 4.4) %. The expression of TLR-4 mRNA were 1.07 ± 0.09, 2.12 ± 0.33, 2.07 ± 0.29, 2.17 ± 0.34, 4.53 ± 0.46. Compared with group A, groups B- E showed significant higher pathology score (P < 0.05) and increased expression of both TLR-4 (P < 0.05) and TLR-4 mRNA (P < 0.05). An significant positive correlation was found between the expression of TLR- 4 and the pathology score (r = 0.785, P < 0.05), and between the expression of TLR- 4 mRNA and the pathology score (r = 0.720, P < 0.05). CONCLUSIONS: TLR-4 may be closely associated with the development of the synovitis of TMJ of rats.