High-frequency low-intensity semiconductor laser irradiation enhances osteogenic differentiation of human cementoblast lineage cells.

PURPOSE: Laser irradiation activates a range of cellular processes in the periodontal components and promotes tissue repair. However, its effect on osteogenic differentiation of human cementoblast lineage cells remains unclear. This study aimed to examine the effects of high-frequency semiconductor laser irradiation on the osteogenic differentiation of human cementoblast lineage (HCEM) cells. METHODS: HCEM cells were cultured to reach 80% confluence and irradiated with a gallium-aluminum-arsenide (Ga-Al-As) semiconductor laser with a pulse width of 200 ns and wavelength of 910 at a dose of 0-2.0 J/cm2. The outcomes were assessed by analyzing the mRNA levels of alkaline phosphatase (ALP), runt-related transcription factor 2 (RUNX2), and type I collagen (COLL1) using real-time polymerase chain reaction (PCR) analysis 24 h after laser irradiation. Cell mineralization was evaluated using ALP activity, calcium deposition, and Alizarin Red staining. RESULTS: The laser-irradiated HCEM cells showed significantly enhanced gene expression levels of ALP, RUNX2, and COLL1 as well as ALP activity and calcium concentration in the culture medium compared with the non-irradiated cells. In addition, enhanced calcification deposits were confirmed in the laser-irradiated group compared with the non-irradiated group at 21 and 28 days after the induction of osteogenic differentiation. CONCLUSION: High-frequency semiconductor laser irradiation enhances the osteogenic differentiation potential of cultured HCEM cells, underscoring its potential utility for periodontal tissue regeneration.

Stem cells derived from human exfoliated deciduous teeth-based media in a rat root resorption model.

OBJECTIVE: Root resorption may occur during orthodontic treatment. Herein, we investigated the effect of a culture supernatant of stem cells derived from human exfoliated deciduous teeth on root resorption. DESIGN: Twelve 8-week-old male Sprague-Dawley rats were used, and their maxillary first molars were pulled with excessive orthodontic force to induce root resorption. On days 1 and 7 after traction initiation, stem cells derived from human exfoliated deciduous teeth and alpha minimum essential medium (control group) were administered. After 14 days, the maxillary bone was evaluated for tooth movement. The expression of osteoprotegerin, receptor activator of nuclear factor κB ligand, tumor necrosis factor α, interleukin 1ß, interleukin 6, and interleukin 17 was evaluated on the compression side and tension side. RESULTS: No significant difference in tooth movement was observed between the two groups. Root resorption decreased in the group administered the culture supernatant compared with in the control. Immunohistochemical staining revealed increased osteoprotegerin expression and decreased receptor activators for nuclear factor κB ligand, tumor necrosis factor α, interleukin 1ß, interleukin 6, and interleukin 17 on the compression side and tension side. CONCLUSIONS: Administration of stem cells derived from human exfoliated deciduous teeth affected the expression of osteoprotegerin, receptor activator of nuclear factor κB ligand, tumor necrosis factor α, interleukin 1ß, interleukin 6 and interleukin 17; hence, these stem cells may inhibit root resorption by regulating their expression.

High-frequency near-infrared semiconductor laser irradiation suppressed experimental tooth movement-induced inflammatory pain markers in the periodontal ligament tissues of rats.

High-frequency near-infrared (NIR) semiconductor laser-irradiation has an unclear effect on nociception in the compressed lateral periodontal ligament region, a peripheral nerve region. This study aimed to investigate the effects of NIR semiconductor laser irradiation, with a power of 120 J, on inflammatory pain markers and neuropeptides induced in the compressed lateral periodontal ligament area during ETM. A NIR semiconductor laser [910 nm wavelength, 45 W maximum output power, 300 mW average output power, 30 kHz frequency, and 200 ns pulse width (Lumix 2; Fisioline, Verduno, Italy)] was used. A nickel-titanium closed coil that generated a 50-g force was applied to the maxillary left-side first molars and incisors in 7-week-old Sprague-Dawley (280-300 g) rats to induce experimental tooth movement (ETM) for 24 h. Ten rats were divided into two groups (ETM + laser, n = 5; ETM, n = 5). The right side of the ETM group (i.e., the side without induced ETM) was evaluated as the untreated group. We performed immunofluorescent histochemistry analysis to quantify the interleukin (IL)-1ß, cyclooxygenase-2 (COX2), prostaglandin E2 (PGE2), and neuropeptide [calcitonin gene-related peptide (CGRP)] expression in the compressed region of the periodontal tissue. Post-hoc Tukey-Kramer tests were used to compare the groups. Compared with the ETM group, the ETM + laser group showed significant suppression in IL-1ß (176.2 ± 12.3 vs. 310.8 ± 29.5; P < 0.01), PGE2 (104.4 ± 14.34 vs. 329.6 ± 36.52; P < 0.01), and CGRP (36.8 ± 4.88 vs. 78.0 ± 7.13; P < 0.01) expression. High-frequency NIR semiconductor laser irradiation exerts significant effects on ETM-induced inflammation. High-frequency NIR semiconductor laser irradiation can reduce periodontal inflammation during orthodontic tooth movement.

S100A8 enhances IL-1ß production from nasal epithelial cells in eosinophilic chronic rhinosinusitis.

BACKGROUND: Chronic rhinosinusitis is classified into eosinophilic chronic rhinosinusitis (ECRS) and non-eosinophilic chronic rhinosinusitis (NECRS). ECRS is a refractory allergic disease involving a variety of immune and epithelial cells. S100A8 is a damage-associated molecular pattern that is closely related to allergic inflammation. However, the pathological implications of S100A8 in ECRS have not been clarified. METHODS: We evaluated the role of S100A8 in the pathogenesis of ECRS. Gene expression profiles of nasal polyps obtained from patients with ECRS or NECRS were evaluated using RNA sequencing. RESULTS: S100A8 was identified as a significantly upregulated gene in nasal polyps associated with ECRS. Immunohistochemistry consistently revealed intense S100A8 staining in nasal polyps from patients with ECRS. Human nasal epithelial cells expressed the receptor for advanced glycation end products and Toll-like receptor 4. Recombinant S100A8 protein induced interleukin-1ß secretion in human nasal epithelial cells. CONCLUSIONS: Our data demonstrate that S100A8 results in production of interleukin-1ß in the nasal epithelium, which may be involved in the pathogenesis of ECRS.

Effects of Human Deciduous Dental Pulp-Derived Mesenchymal Stem Cell-Derived Conditioned Medium on the Metabolism of HUVECs, Osteoblasts, and BMSCs.

In this study, we assessed the effects of human deciduous dental pulp-derived mesenchymal stem cell-derived conditioned medium (SHED-CM) on the properties of various cell types. The effects of vascular endothelial growth factor (VEGF) in SHED-CM on the luminal architecture, proliferative ability, and angiogenic potential of human umbilical vein endothelial cells (HUVECs) were determined. We also investigated the effects of SHED-CM on the proliferation of human-bone-marrow mesenchymal stem cells (hBMSCs) and mouse calvarial osteoblastic cells (MC3T3-E1) as well as the expression of ALP, OCN, and RUNX2. The protein levels of ALP were examined using Western blot analysis. VEGF blockade in SHED-CM suppressed the proliferative ability and angiogenic potential of HUVECs, indicating that VEGF in SHED-CM contributes to angiogenesis. The culturing of hBMSCs and MC3T3-E1 cells with SHED-CM accelerated cell growth and enhanced mRNA expression of bone differentiation markers. The addition of SHED-CM enhanced ALP protein expression in hBMSCs and MT3T3-E1 cells compared with that of the 0% FBS group. Furthermore, SHED-CM promoted the metabolism of HUVECs, MC3T3-E1 cells, and hBMSCs. These findings indicate the potential benefits of SHED-CM in bone tissue regeneration.

Longitudinal effects of estrogen on mandibular growth and changes in cartilage during the growth period in rats.

Estrogen is a steroid hormone that induces skeletal growth and affects endochondral ossification of the long tubular bone growth plate during the growth period. However, the effects of estrogen on endochondral ossification of the mandibular condylar cartilage are unclear. In this study, ovariectomized Wistar/ST rats were used to investigate the longitudinal effects of estrogen on mandibular growth. The rats were administered different doses of estrogen. Longitudinal micro-computed tomographic scanning, histological staining and ELISA on plasma growth hormone were performed to examine the effects of estrogen on mandibular growth. The results showed that mandibular growth was suppressed throughout the growth period by estrogen in a dose-dependent manner. In addition, long-term administration of a high dose of estrogen to the rats resulted in significant increase in growth hormone throughout the growth period, significant circularization of cell nuclei in the proliferative layer, intensely staining cartilage matrix in the subchondral bone, and significant suppression of estrogen receptor (ER) alpha and beta expression in the mandibular cartilage. However, regardless of estrogen concentration, in the posterior part of the mandibular cartilage, ER expression extended to both the hypertrophic and proliferative layers. These results indicate that estrogen suppresses mandibular growth throughout the growth period. Additionally, it influences endochondral ossification via its effect on ERs.

Co-Treatment with Steroid and Dupilumab for Eosinophilic Chronic Rhinosinusitis after Eosinophilic Pneumonitis Caused by Dupilumab.

Eosinophilic chronic rhinosinusitis (ECRS) is a Type 2 inflammatory disease that manifests as chronic inflammation of the paranasal sinus. IL-4/IL-13 receptor monoclonal antibodies (dupilumab) to suppress Type 2 inflammation have become a good treatment option for patients who are refractory to surgery. Most patients respond normally, although significant side effects such as eosinophilic pneumonia may occur, requiring discontinuation of dupilumab. Here, we present a case in which dupilumab administration caused a side-effect of eosinophilic pneumonia. A 65-year-old woman presented with nasal obstruction and olfactory dysfunction due to a nasal polyp. Her symptoms temporarily improved with dupilumab; however, dupilumab was discontinued due to eosinophilic pneumonia. Discontinuation of dupilumab resulted in the rapid resolution of eosinophilic pneumonia and reappearance of nasal polyps. We, therefore, resumed dupilumab treatment in combination with low-dose steroids; eosinophilic pneumonia did not flare up, and the nasal polyps shrank steadily. There is no established treatment strategy in cases where a side effect of eosinophilic pneumonia arises while treating ECRS with dupilumab. Based on the described case, we recommend that a combination of a low-dose steroids and dupilumab be considered as a treatment option to counter the side-effect of eosinophilic pneumonia induced by dupilumab alone.

Combination of Carbonate Hydroxyapatite and Stem Cells from Human Deciduous Teeth Promotes Bone Regeneration by Enhancing BMP-2, VEGF and CD31 Expression in Immunodeficient Mice.

The objective of this study was to clarify the efficiency of a combination of stem cells from human deciduous teeth and carbonate apatite in bone regeneration of calvarial defects. Immunodeficient mice (n = 5 for each group/4 groups) with artificial calvarial bone defects (5 mm in diameter) were developed, and stem cells from human deciduous teeth (SHEDs) and carbonate hydroxyapatite (CAP) granules were transplanted with an atelocollagen sponge as a scaffold. A 3D analysis using microcomputed tomography, and 12 weeks after transplantation, histological and immunohistochemical evaluations of markers of bone morphogenetic protein-2 (BMP-2), vascular endothelial growth factor (VEGF), and cluster of differentiation (CD) 31 were performed. In the 3D analysis, regenerated bone formation was observed in SHEDs and CAP, with the combination of SHEDs and CAP showing significantly greater bone regeneration than that in the other groups. Histological and immunohistochemical evaluations showed that combining SHEDs and CAP enhanced the expression of BMP-2, VEGF, and CD31, and promoted bone regeneration. This study demonstrates that the combination of SHEDs and CAP transplantation may be a promising tool for bone regeneration in alveolar defects.

Effects of high-frequency near infrared laser irradiation on experimental tooth movement-induced pain in rats.

Discomfort and dull pain are known side effects of orthodontic treatment. Pain is expected to be reduced by near-infrared (NIR) lasers; however, the mechanism underlying effects of short-pulse NIR lasers in the oral and maxillofacial area remains unclear. This study aimed to examine the effects of high-frequency NIR diode laser irradiation on pain during experimental tooth movement (ETM) on 120 J. NIR laser with 910 nm wavelength, 45 W maximum output power, 300 mW average output power, and 200 ns pulse width (Lumix 2; (Lumix 2; Fisioline, Verduno CN, Italy) was used for the experiment. A nickel-titanium-closed coil was used to apply a 50-gf force between the maxillary left-side first molar and incisor in 7-week-old Sprague-Dawley rats (280-300 g) to induce ETM. We measured facial-grooming frequency and vacuous chewing movement (VCM) period between laser-irradiation and ETM groups. We performed immunofluorescent histochemistry analysis to quantify levels of Iba-1, astrocytes, and c-fos protein-like immunoreactivity (Fos-IR) in the trigeminal spinal nucleus caudalis (Vc). Compared with the ETM group, the laser irradiation group had significantly decreased facial-grooming frequency (P = 0.0036), VCM period (P = 0.043), Fos-IR (P = 0.0028), Iba-1 levels (P = 0.0069), and glial fibrillary acidic protein (GFAP) levels (P = 0.0071). High-frequency NIR diode laser irradiation appears to have significant analgesic effects on ETM-induced pain, which involve inhibiting neuronal activity, microglia, and astrocytes, and it inhibits c-fos, Iba-1, and GFAP expression, reducing ETM-induced pain in rats. High-frequency NIR diode laser application could be applied to reduce pain during orthodontic tooth movement.

Organized Hematoma after Intra-Arterial Chemoradiotherapy for Maxillary Sinus Cancer: A Case Report.

An organized hematoma (OH) is a relatively rare benign lesion of the paranasal sinuses. Traditionally, it has been reported to occur following trauma, surgery, and sinus hemorrhagic lesions and in various bleeding predispositions. OHs are sometimes difficult to differentiate from malignancy because of the similar clinical symptoms and bone destruction. It is especially difficult when OHs occur in the same location as the primary tumor after treatment of a malignant tumor. In this paper, we report two cases of OH that occurred after intra-arterial chemoradiotherapy (IACRT) for maxillary sinus cancer. In one case, FDG accumulation was found in PET/CT and suspected to be a cancer recurrence. However, the postoperative pathology showed no malignant findings. This suggests that OH may show accumulation on 18 F-fluorodeoxyglucose positron emission tomography (FDG-PET). In both cases, bleeding from the maxillary sinus continued after surgery. In one case, recurrence was observed, and in the other, nasal irrigation prevented the pooling of blood in the maxillary sinus, and no recurrence was observed. These cases suggest that OH after IACRT may easily recur because the bleeding continues even after surgery. In such cases, nasal irrigation or preoperative embolization may be helpful to avoid recurrence.

High-frequency near-infrared diode laser irradiation suppresses IL-1ß-induced inflammatory cytokine expression and NF-κB signaling pathways in human primary chondrocytes.

Osteoarthritis (OA) and rheumatoid arthritis (RA) are common inflammation-associated cartilage degenerative diseases. Recent studies have shown that low-level diode laser treatment can reduce inflammatory cytokine expressions in cartilage. We recently reported that high-frequency low-level diode laser irradiation attenuates matrix metalloproteinases (MMPs) expression in human primary chondrocytes. However, the molecular mechanism underlying the effect of high-frequency low-level diode laser on chondrocytes remains unclear. Therefore, we aimed to elucidate the effect of high-frequency low-level diode laser irradiation on inflammatory cytokine expression in human primary chondrocytes. Normal human articular chondrocytes were treated with recombinant interleukin-1 beta (IL-1ß) for 30 min or 24 h and irradiated with a high-frequency NIR diode laser at 8 J/cm2. The expression of IL-1ß, interleukin-6, and tumor necrosis factor-alpha was assessed using western blot analysis. To evaluate the nuclear factor-kappa B (NF-κB) signaling pathway, the phosphorylation, translocation, and DNA-binding activity of NF-κB were detected using western blot analysis, immunofluorescence analysis, electrophoretic mobility shift assay, and enzyme-linked immunosorbent assay analysis. High-frequency low-level diode laser irradiation decreased inflammatory cytokine expression in IL-1ß-treated chondrocytes. Moreover, high-frequency low-level diode laser irradiation decreased the phosphorylation, nuclear translocation, and DNA-binding activity of NF-κB in the IL-1ß-treated state. However, irradiation alone did not affect NF-κB activity. Thus, high-frequency low-level diode laser irradiation at 8 J/cm2 can reduce inflammatory cytokine expressions in normal human articular chondrocytes through NF-κB regulation. These findings indicate that high-frequency low-level diode laser irradiation may reduce the expression of inflammatory cytokines in OA and RA.

A Case of Endonasal Endoscopic Surgery for Intraorbital Metastasis of Gastric Ring Cell Carcinoma.

Gastric signet ring cell carcinoma has well-known metastatic features, including peritoneal dissemination and carcinomatous lymphangitis of the lung, but no intraorbital metastases were reported previously. A woman in her 60s developed left eye pain, sudden vision loss, and headache 12 years after gastric cancer treatment. Symptoms did not improve despite steroid pulses. Craniotomy showed no malignant findings. The patient was referred to our department for symptomatic relief and biopsy due to the lack of a definitive diagnosis and no improvement in her ocular pain. Endonasal endoscopic surgery was performed for diagnostic purposes and to relieve symptoms through orbital decompression. Preoperative computed tomography examination revealed a tumor at the left medial orbit, extending to the orbital apex. Orbital decompression through the open left medial orbital wall was performed with biopsy of the intraorbital tumor. Pathological findings were consistent with metastatic signet ring cell carcinoma. Pain and subjective improvement of visual acuity were noted the day after surgery. Twelve months postoperatively, diplopia remains, but there has been no worsening of symptoms.

Skull Base Metastasis of Breast Cancer With Oculomotor and Trochlear Nerve Palsy.

Skull base metastatic tumors are rare. Breast cancer in particular can cause bone metastases after a long period of time. A 70-year-old woman presented with multiple cranial nerve palsy. Magnetic resonance imaging revealed a lesion that extended from the orbit to the base of the skull, and the patient was referred to our department. Ophthalmological evaluation showed left visual acuity impairment, left oculomotor nerve palsy, and left trochlear nerve palsy. Endoscopic biopsy performed 5 years after the completion of breast cancer treatment revealed skull base metastases. In unilateral multiple cranial nerve palsy, the possibility of skull base metastases should be considered.

Isolated sphenoid sinus opacification is often asymptomatic and is not referred for otolaryngology consultation.

Isolated sphenoid sinus opacifications (ISSOs) are clinically important because they can lead to serious complications. However, some patients with ISSOs are asymptomatic, and not all patients are properly referred to the otolaryngology department. Because past studies of ISSOs focused only on patients who received treatment, in this study we selected ISSO cases based on radiology reports, then determined whether these patients had symptoms and were appropriately referred for specialty care. We conducted a retrospective analysis of data collected from patients who underwent computed tomography or magnetic resonance imaging from January 2007 to March 2017 at Osaka General Medical Center. We searched for the terms "sphenoid" or "sphenoidal" using F-REPORT to identify patients who had a sphenoid disease. We checked all selected images and diagnosed ISSOs. Examination of 1115 cases revealed 223 cases of ISSOs, of whom 167 (74.9%) were asymptomatic. We categorized patients with ISSOs into four groups: inflammation, mucocele, fungal diseases, and unclassifiable; the final category was used when edges were irregular or complete opacity was encountered. In the unclassifiable group, the majority of cases required otolaryngology consultation, but 37 of 47 unclassifiable patients did not have an otolaryngology visit. ISSOs are often identified by chance on imaging tests performed by non-otolaryngologists. However, our study revealed that many patients with ISSOs who should be treated by otolaryngologists were not referred to the otolaryngology department. Accordingly, it is important to promote awareness of the disease among other types of clinicians.

Examination of the effect of combined use of Er:YAG laser irradiation and mechanical force loading on bone metabolism using primary human gingival fibroblasts.

Prolonged treatment and painful tooth movement are major problems for patients undergoing orthodontic treatment. Accelerating the movement of teeth leads to shortening of the treatment period, so various studies on the movement of teeth have been conducted in the field of orthodontics. In previous studies, we performed a fiber incision-like fiberotomy using an Er:YAG laser in rats and confirmed acceleration of tooth movement. Therefore, in this study, the effect of Er:YAG laser irradiation on human gingival fibroblasts was investigated in vitro. Human gingival fibroblasts (2.0 × 105 cells) were seeded in a 6-well plate and reached 80% confluence 24 h later. A control group not undergoing any irradiation and 3 groups undergoing laser irradiation at 0.6 W, 1.0 W, and 1.2 W were investigated. Laser irradiation was performed 24 h after cell seeding. The cells were then recovered 24 h later, and the cyclooxygenase-2 (COX-2), interleukin-1ß (IL-1ß), tumor necrosis factor-α (TNF-α), bone morphogenetic protein-2 (BMP-2), and BMP-4 genes were confirmed by PCR. In addition, a control group not undergoing any procedures, a group undergoing only Er:YAG laser irradiation, a group undergoing only centrifugal loading, and a group undergoing both Er:YAG laser irradiation and centrifugal force loading were investigated. After 24 h, cells were collected and PCR was performed. Twenty-four hours after laser irradiation, gene expressions were examined by quantitative RT-PCR, which showed that the gene expressions of COX-2, IL-1ß, TNF-α, BMP-2, and BMP-4 increased depending on the amount of irradiation energy, with the largest value at 1.2 W. Gene expressions of COX-2, IL-1ß, TNF-α, BMP-2, and BMP-4 were significantly higher in the laser with centrifugal load group than in the load group. These results suggest that genes related to bone metabolism are activated in human gingival fibroblasts when mechanical stimulation and laser irradiation are combined. This helps to elucidate the effects of Er:YAG laser irradiation during tooth movement.

Baicalin inhibits root resorption during tooth movement in a rodent model.

OBJECTIVE: Baicalin mediates bone metabolism and has shown protective activity against periodontal tissue damage in a rat model of periodontitis. Therefore, we hypothesized that baicalin may inhibit the root resorption that occurs during orthodontic tooth movement and examined its effect on the histological changes in periodontal tissue that occur during tooth movement. METHODS: First molars of rats were subjected to traction using excessive orthodontic force to produce a root resorption model. Rats in the baicalin group received baicalin for 3 weeks during tooth movement, and the amount of first molar movement on day 21 after the initiation of traction was measured by three-dimensional micro-computed tomography analysis. After tooth movement, tissue samples from the mesial and tension sides were collected, and successive horizontal sections were prepared and examined using hematoxylin-eosin and tartrate-resistant acid phosphatase (TRAP) staining and immunohistochemical staining for the receptor activator of NF-kB ligand (RANKL) and osteoprotegerin (OPG). The severity of root resorption was also determined by histological analysis. RESULTS: There was no significant intergroup difference in tooth movement during the experimental exaggerated tooth movement. In comparison with the control group, the baicalin-treated group showed increased OPG expression, suppressed RANKL expression, and significantly fewer TRAP-positive cells in the first molars. The root resorption area was significantly smaller in the baicalin group. CONCLUSIONS: Treatment with baicalin prevented root resorption without preventing tooth movement. Baicalin may be useful for the management of root resorption during orthodontic treatment.

High-Frequency Near-Infrared Diode Laser Irradiation Attenuates IL-1ß-Induced Expression of Inflammatory Cytokines and Matrix Metalloproteinases in Human Primary Chondrocytes.

High-frequency near-infrared diode laser provides a high-peak output, low-heat accumulation, and efficient biostimulation. Although these characteristics are considered suitable for osteoarthritis (OA) treatment, the effect of high-frequency near-infrared diode laser irradiation in in vitro or in vivo OA models has not yet been reported. Therefore, we aimed to assess the biological effects of high-frequency near-infrared diode laser irradiation on IL-1ß-induced chondrocyte inflammation in an in vitro OA model. Normal Human Articular Chondrocyte-Knee (NHAC-Kn) cells were stimulated with human recombinant IL-1ß and irradiated with a high-frequency near-infrared diode laser (910 nm, 4 or 8 J/cm2). The mRNA and protein expression of relevant inflammation- and cartilage destruction-related proteins was analyzed. Interleukin (IL) -1ß treatment significantly increased the mRNA levels of IL-1ß, IL-6, tumor necrosis factor (TNF) -α, matrix metalloproteinases (MMP) -1, MMP-3, and MMP-13. High-frequency near-infrared diode laser irradiation significantly reduced the IL-1ß-induced expression of IL-1ß, IL-6, TNF-α, MMP-1, and MMP-3. Similarly, high-frequency near-infrared diode laser irradiation decreased the IL-1ß-induced increase in protein expression and secreted levels of MMP-1 and MMP-3. These results highlight the therapeutic potential of high-frequency near-infrared diode laser irradiation in OA.

Pathological and therapeutic implications of eosinophil-derived semaphorin 4D in eosinophilic chronic rhinosinusitis.

BACKGROUND: Eosinophilic chronic rhinosinusitis (ECRS) is a subtype of chronic rhinosinusitis. Clinical markers for ECRS disease activity and treatment strategies have not been sufficiently established. Although semaphorins are originally identified as neuronal guidance factors, it is becoming clear that they play key roles in immune regulation and inflammatory diseases. OBJECTIVE: We sought to investigate the pathological functions and therapeutic potential of semaphorin 4D (SEMA4D) in ECRS. METHODS: Serum soluble SEMA4D levels in patients with paranasal sinus diseases were measured by ELISA. The expression of SEMA4D in blood cells and nasal polyp tissues was assessed by flow cytometry and immunohistochemistry, respectively. Generation of soluble SEMA4D was evaluated in matrix metalloproteinase-treated eosinophils. Endothelial cells were stimulated with recombinant SEMA4D, followed by eosinophil transendothelial migration assays. Allergic chronic rhinosinusitis was induced in mice using Aspergillus protease with ovalbumin. The efficacy of treatment with anti-SEMA4D antibody was evaluated histologically and by nasal lavage fluid analysis. RESULTS: Serum soluble SEMA4D levels were elevated in patients with ECRS and positively correlated with disease severity. Tissue-infiltrated eosinophils in nasal polyps from patients with ECRS stained strongly with anti-SEMA4D antibody. Cell surface expression of SEMA4D on eosinophils from patients with ECRS was reduced, which was due to matrix metalloproteinase-9-mediated cleavage of membrane SEMA4D. Soluble SEMA4D induced eosinophil transendothelial migration. Treatment with anti-SEMA4D antibody ameliorated eosinophilic infiltration in sinus tissues and nasal lavage fluid in the ECRS animal model. CONCLUSIONS: Eosinophil-derived SEMA4D aggravates ECRS. Levels of serum SEMA4D reflect disease severity, and anti-SEMA4D antibody has therapeutic potential as a treatment for ECRS.

Molecular biological and histological effects of Er:YAG laser irradiation on tooth movement.

The aim of this study was to evaluate the effects of a fiberotomy-like procedure using Er:YAG laser irradiation on the velocity of orthodontic tooth movement. To produce experimental tooth movement in rats, orthodontic force was applied to the upper first molars with a nickel-titanium closed coil. The right molars were irradiated with an Er:YAG laser while the non-irradiated left molars were used as controls. The rats were sacrificed at 4 weeks after the start of tooth movement and the distance between the mesial side of the second molar and the distal side of the upper first molar was measured on CT images. The amount of tooth movement was significantly greater in the irradiation group than in the control group. The TRAP-positive nuclei count at the pressure site was higher in the laser-irradiation group than in the control group. Expression of RANKL and ALP was higher at the mesial-coronal pressure site in the laser-irradiation group than in the control group. In addition, expression of OPG was higher at the pressure site in the control group than in the laser-irradiation group. These results suggest that a fiberotomy-like procedure using an Er:YAG laser stimulates osteoclasts and osteoblasts and may promote bone metabolism in the context of experimental tooth movement.