Jae-Kwang Jung

5‐HT1B receptors inhibit glutamate release from primary afferent terminals in rat medullary dorsal horn neurons

BACKGROUND AND PURPOSE Although 5‐HT1B receptors are expressed in trigeminal sensory neurons, it is still not known whether these receptors can modulate nociceptive transmission from primary afferents onto medullary dorsal horn neurons.

Contribution of Mesenchymal Proliferation in Tooth Root Morphogenesis

In mouse tooth development, the roots of the first lower molar develop after crown formation to form 2 cylindrical roots by post-natal day 5. This study compared the morphogenesis and cellular events of the mesial-root-forming (MRF) and bifurcation-forming (BF) regions, located in the mesial and center of the first lower molar, to better define the developmental mechanisms involved in multi-rooted tooth formation. We found that the mesenchyme in the MRF showed relatively higher proliferation than the bifurcation region. This suggested that spatially regulated mesenchymal proliferation is required for creating cylindrical root structure. The mechanism may involve the mesenchyme forming a physical barrier to epithelial invagination of Hertwig’s epithelial root sheath. To test these ideas, we cultured roots in the presence of pharmacological inhibitors of microtubule and actin polymerization, nocodazole and cytochalasin-D. Cytochalasin D also inhibits proliferation in epithelium and mesenchyme. Both drugs resulted in altered morphological changes in the tooth root structures. In particular, the nocodazole- and cytochalasin-D-treated specimens showed a loss of root diameter and formation of a single-root, respectively. Immunolocalization and three-dimensional reconstruction results confirmed these mesenchymal cellular events, with higher proliferation in MRF in multi-rooted tooth formation.

The presence of altered craniocervical posture and mobility in smartphone-addicted teenagers with temporomandibular disorders

[Purpose] Smartphones are widely used by teenagers and adults for various purposes. As teenagers use smartphones more actively than adults, they are more prone to be addicted to smartphones. Furthermore, excessive usage of smartphones can lead to various psychosocial and physical symptoms. [Subjects and Methods] One hundred teenage subjects were recruited and divided into normal and addiction groups, based on the criteria of the smartphone addiction scale-short version questionnaire. Craniocervical posture and mobility were examined by lateral cephalometric analysis and a cervical range of motion instrument. [Results] Cephalometric analysis showed no significant difference in the craniocervical angles of the resting positions of the two groups. However, measurement using an inclinometer revealed a significantly flexed cervical posture while using smartphones and decreased cervical range of motion in the smartphone-addicted teenagers. The clinical profile of temporomandibular disorders revealed that muscular problems were more frequently presented in the smartphone-addicted teenagers. [Conclusion] These findings suggest that smartphone addiction has a negative influence on craniocervical posture and mobility. Further, it can be postulated that smartphone addiction among teenagers may have contributed to the occurrence of myogenous temporomandibular disorders. In conclusion, smartphone-addicted teenagers may be more frequently subjected to muscular disturbance in the craniocervical area, which probably affects the pathologic process of temporomandibular disorders in teenagers.

Immunolocalization patterns of cytokeratins during salivary acinar cell development in mice

Embryonic development of the mouse salivary glands begins with epithelial thickening and continues with sequential changes from the pre-bud to terminal bud stages. After birth, morphogenesis proceeds, and the glands develop into a highly branched epithelial structure that terminates with saliva-producing acinar cells at the adult stage. Acinar cells derived from the epithelium are differentiated into serous, mucous, and seromucous types. During differentiation, cytokeratins, intermediate filaments found in most epithelial cells, play vital roles. Although the localization patterns and developmental roles of cytokeratins in different epithelial organs, including the mammary glands, circumvallate papilla, and sweat glands, have been well studied, their stage-specific localization and morphogenetic roles during salivary gland development have yet to be elucidated. Therefore, the aim of this study was to determine the stage and acinar cell type-specific localization pattern of cytokeratins 4, 5, 7, 8, 13, 14, 18, and 19 in the major salivary glands (submandibular, sublingual, and parotid glands) of the mouse at the E15.5, PN0, PN10, and adult stages. In addition, cell physiology, including cell proliferation, was examined during development via immunostaining for Ki67 to understand the cellular mechanisms that govern acinar cell differentiation during salivary gland morphogenesis. The distinct localization patterns of cytokeratins in conjunction with cell physiology will reveal the roles of epithelial cells in salivary gland formation during the differentiation of serous, mucous or seromucous salivary glands.

Involvement of PI3K and PKA pathways in mouse tongue epithelial differentiation.

In mice, tongue epithelial differentiation is mainly regulated by the interactions among various signalling molecules including Fgf signalling pathways. However, the subsequent signalling modulations for epithelial maturation, initiated by Fgf signalling, remain to be elucidated. Therefore, we employed an in vitro tongue organ cultivation system along with the applications of various pharmacological inhibitors against the intracellular signalling molecules of Fgf signalling pathways, including H89, LY294002, PD98059, and U0126. Following treatments with LY294002 and H89, inhibitors for PI3K and PKA, respectively, the decreased thickness of the tongue epithelium was observed along with the alteration in cell proliferative and apoptotic patterns. Meanwhile, cultivated tongues treated with MEK inhibitor U0126 or PD98059 showed significantly decreased cell proliferation in the tongue epithelium and the mesenchyme. Based on these results, we suggest that the tongue epithelium is differentiated into multiple epithelial cell layers via the PI3K and PKA pathways in tissue-specific manner during the epithelial-mesenchymal interactions.

Gene profiling involved in fate determination of salivary gland type in mouse embryogenesis

Salivary gland (SG) development involves dynamic epithelial-mesenchymal interactions resulting in the formation of highly branched epithelial structures that produce and secrete saliva. The SG epithelium differentiates into saliva-producing terminal buds, i.e., acini, and transporting ducts. Most studies on the salivary gland have focused on branching morphogenesis; however, acinar cell differentiation underlying the determination of serous or mucous salivary glands is unclear. The objective of this study was to identify the mesenchymal signaling molecules involved in the epithelial differentiation of the salivary gland type as serous or mucous. Salivary glands undergoing stage-specific development, including the parotid gland (PG) and the sublingual gland (SLG) at embryonic day 14.5 (E14.5) were dissected. The glands were treated with dispase II to separate the epithelium and the mesenchyme. RNA from mesenchyme was processed for microarray analysis. Thereafter, microarray data were analyzed to identify putative candidate molecules involved in salivary gland differentiation and confirmed via quantitative reverse transcription polymerase chain reaction. The microarray analysis revealed the expression of 31,873 genes in the PG and SLG mesenchyme. Of the expressed genes 21,026 genes were found to be equally expressed (Fold change 1.000) in both PG and SLG mesenchyme. The numbers of genes expressed over onefold in the PG and SLG mesenchyme were found to be 5247 and 5600 respectively. On limiting the fold-change cut off value over 1.5 folds, only 214 and 137 genes were expressed over 1.5 folds in the PG and the SLG mesenchyme respectively. Our findings suggest that differential expression patterns of the mesenchymal signaling molecules are involved in fate determination of the salivary acinar cell types during mouse embryogenesis. In the near future, functional evaluation of the candidate genes will be performed using gain- and loss-of-function mutation studies during in vitro organ cultivation.

Loss of toll-like receptor 3 aggravates hepatic inflammation but ameliorates steatosis in mice

The importance of toll-like receptor (TLR) 4 in the pathogenesis of steatohepatitis has been well documented; however, little is known about the role of TLR3. In this study, we determined whether the depletion of TLR3 modulated hepatic injury in mice and further aimed to provide mechanistic insights into the TLR3-mediated modulation of diet-induced hepatic inflammation and fat accumulation. Hepatic steatosis and inflammatory response were induced by feeding wild-type (WT) or TLR3 knockout mice a high-fat diet for 8 weeks. Primary liver resident cells, including hepatocytes, Kupffer cells, and hepatic stellate cells (HSCs), were treated with palmitic acid. TLR3 knockout mice fed a high-fat diet showed severe hepatic inflammation accompanied by nuclear factor-κB and IRF3 activation, which is mainly induced by the activation of Kupffer cells. Decreased TLR4 expression was restored in hepatic mononuclear cells and Kupffer cells in TLR3 knockout mice compared to that in the WT. Moreover, hepatic steatosis was decreased in TLR3 knockout mice. Hepatocytes from TLR3 knockout mice exhibited reduced expression of cannabinoid receptors. HSCs from TLR3 knockout mice showed decreased expression of the enzymes involved in endocannabinoid synthesis. In conclusion, this study suggests that the selective modulation of TLR3 could be a novel therapeutic target for the treatment of hepatic inflammation and steatosis.

Developmental roles of Meox2 in palatal mucosa differentiation

During palatogenesis, the anterior palate is covered with ortho or parakeratinized epithelium while the posterior palate is covered with non-keratinized epithelium. To elucidate the developmental mechanisms underlying these region-specific differentiation patterns of palatal epithelium along the antero-posterior axis, we employed the tissue recombination assay during in vitro organ cultivation of the developing palate at E16 for 2 days. The recombination assay results revealed that epithelial differentiation with specific localization patterns of Cytokeratin10 and Ki67 are modulated by mesenchymal tissues. Based on these results, we examined the underlying signaling regulations that modulate epithelial differentiation, using laser microdissection and genome wide screening. Our screening data suggested Meox2 (Mesenchyme homeobox 2) to be a key regulator that controls epithelial differentiation in the mesenchymal tissue. To examine the developmental function of Meox2, we employed in vitro organ cultivation along with the knockdown and overexpression of Meox2 using siRNA andMeox2 overexpression vector, respectively, at E14.5 for 2 and 4 days. After 2-day cultivation, we examined the altered expression patterns of related signaling molecules such as Shh and Bmp, using in situ hybridization and RT-qPCR. After 4-day cultivation, we examined the altered histogenesis and localization patterns of Cytokeratin10 and Ki67. Based on the restricted and specific expression of candidate mesenchymal genes and the results of the recombination assay, we conclude that posteriorly expressed Meox2 is involved in the determination of non-keratinized epithelial differentiation through complex signaling regulations in mice palatogenesis.

Clinical Consideration of Trigger Point Injection/Dry Needling Therapy: A Narrative Review

Received September 8, 2017 Revised September 13, 2017 Accepted September 14, 2017 Myogenous temporomandibular disorder is a collective term for pathologic conditions of the masticatory muscles, mainly characterized by pain and dysfunction associated with various pathophysiological processes. Among the subtypes of myogenous temporomandibular disorder, myofascial pain is one of the most common muscle disorders, characterized by the presence of trigger points (TrPs). Various modalities, such as ultrasound, manipulative therapy, sprayand-stretch technique, transcutaneous electrical nerve stimulation, injection/dry needling, and low-level laser therapy are used to inactivate TrPs. Needling/injection on the TrPs is one of the most common treatments for myofascial pain. Despite the evidence, there is continued controversy over defining the biological and clinical characteristics of TrPs and the efficacy of injection/dry needling. This review discusses the current concept of injection/needling to relieve TrPs.

Oral Submucous Fibrosis in a 26-Year-Old Sri Lankan Man Living in South Korea

Received August 22, 2017 Revised September 14, 2017 Accepted September 14, 2017 Oral submucous fibrosis (OSF) is a premalignant condition characterized by juxtaepithelial fibrosis of the oral cavity. The clinical manifestations include burning sensation to spicy food, blanched oral mucosa with palpable fibrous bands, trismus, depapillation of tongue, and dry mouth. As OSF is predominantly seen in people of the Indian subcontinent, cases of this disease have been rarely reported in South Korea. We present a case of OSF in a Sri Lankan man living in South Korea and emphasize the importance of enhancing knowledge of this disease while the number of immigrants is increasing.