Reduction of Osteoclastic Differentiation of Raw 264.7 Cells by EMF Exposure through TRPV4 and p-CREB Pathway.

In this study, we investigated the effect of EMF exposure on the regulation of RANKL-induced osteoclast differentiation in Raw 264.7 cells. In the EMF-exposed group, the cell volume did not increase despite RANKL treatment, and the expression levels of Caspase-3 remained much lower than those in the RANKL-treated group. TRAP and F-actin staining revealed smaller actin rings in cells exposed to EMF during RANKL-induced differentiation, indicating that EMF inhibited osteoclast differentiation. EMF-irradiated cells exhibited reduced mRNA levels of osteoclastic differentiation markers cathepsin K (CTSK), tartrate-resistant acid phosphatase (TRAP), and matrix metalloproteinase 9 (MMP-9). Furthermore, as measured by RT-qPCR and Western blot, EMF induced no changes in the levels of p-ERK and p-38; however, it reduced the levels of TRPV4 and p-CREB. Overall, our findings indicate that EMF irradiation inhibits osteoclast differentiation through the TRPV4 and p-CREB pathway.

Induction of PLXNA4 Gene during Neural Differentiation in Human Umbilical-Cord-Derived Mesenchymal Stem Cells by Low-Intensity Sub-Sonic Vibration.

Human umbilical-cord-derived mesenchymal stem cells (hUC-MSC) are a type of mesenchymal stem cells and are more primitive than other MSCs. In this study, we identify novel genes and signal-activating proteins involved in the neural differentiation of hUC-MSCs induced by Low-Intensity Sub-Sonic Vibration (LISSV). RNA sequencing was used to find genes involved in the differentiation process by LISSV. The changes in hUC-MSCs caused by LISSV were confirmed by PLXNA4 overexpression and gene knockdown through small interfering RNA experiments. The six genes were increased among genes related to neurons and the nervous system. One of them, the PLXNA4 gene, is known to play a role as a guide for axons in the development of the nervous system. When the PLXNA4 recombinant protein was added, neuron-related genes were increased. In the PLXNA4 gene knockdown experiment, the expression of neuron-related genes was not changed by LISSV exposure. The PLXNA4 gene is activated by sema family ligands. The expression of SEMA3A was increased by LISSV, and its downstream signaling molecule, FYN, was also activated. We suggest that the PLXNA4 gene plays an important role in hUC-MSC neuronal differentiation through exposure to LISSV. The differentiation process depends on SEMA3A-PLXNA4-dependent FYN activation in hUC-MSCs.

Induced Neurodifferentiation of hBM-MSCs through Activation of the ERK/CREB Pathway via Pulsed Electromagnetic Fields and Physical Stimulation Promotes Neurogenesis in Cerebral Ischemic Models.

Stroke is among the leading causes of death worldwide, and stroke patients are more likely to live with permanent disabilities even after treatment. Several treatments are being developed to improve the quality of life of patients; however, these treatments still have important limitations. Our study thus sought to evaluate the neural differentiation of human bone marrow mesenchymal stem cells (hBM-MSCs) at various pulsed electromagnetic field (PEMF) frequencies. Furthermore, the effects of selected frequencies in vivo were also evaluated using a mouse ischemia stroke model. Cell proliferation decreased by 20% in the PEMF group, as demonstrated by the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide (MTT) assay, and lactate dehydrogenase (LDH) secretion increased by approximately 10% in an LDH release assay. Fluorescence-activated cell sorting (FACS) analysis demonstrated that CD73 and CD105 were downregulated in the PEMF group at 60 Hz. Moreover, microtubule-associated protein 2 (MAP-2) and neurofilament light chain (NF-L) were upregulated in cell cultures at 60 and 75 Hz. To assess the effects of PEMF in vivo, cerebral ischemia mice were exposed to a PEMF at 60 Hz. Neural-related proteins were significantly upregulated in the PEMF groups compared with the control and cell group. Upon conducting rotarod tests, the cell/PEMF group exhibited significant differences in motor coordination at 13 days post-treatment when compared with the control and stem-cell-treated group. Furthermore, the cell and cell/PEMF group exhibited a significant reduction in the expression of matrix metalloproteinase-9 (MMP-9), tumor necrosis factor-alpha (TNF-α) and interferon-gamma (IFN-γ) in the induced ischemic area compared with the control. Collectively, our findings demonstrated that PEMFs at 60 and 75 Hz could stimulate hBM-MSCs neural differentiation in vitro, in addition to promoting neurogenesis to enhance the functional recovery process by reducing the post-stroke inflammatory reaction.

Urine-Derived Stem Cell-Secreted Klotho Plays a Crucial Role in the HK-2 Fibrosis Model by Inhibiting the TGF-ß Signaling Pathway.

Renal fibrosis is an irreversible and progressive process that causes severe dysfunction in chronic kidney disease (CKD). The progression of CKD stages is highly associated with a gradual reduction in serum Klotho levels. We focused on Klotho protein as a key therapeutic factor against CKD. Urine-derived stem cells (UDSCs) have been identified as a novel stem cell source for kidney regeneration and CKD treatment because of their kidney tissue-specific origin. However, the relationship between UDSCs and Klotho in the kidneys is not yet known. In this study, we discovered that UDSCs were stem cells that expressed Klotho protein more strongly than other mesenchymal stem cells (MSCs). UDSCs also suppressed fibrosis by inhibiting transforming growth factor (TGF)-ß in HK-2 human renal proximal tubule cells in an in vitro model. Klotho siRNA silencing reduced the TGF-inhibiting ability of UDSCs. Here, we suggest an alternative cell source that can overcome the limitations of MSCs through the synergetic effect of the origin specificity of UDSCs and the anti-fibrotic effect of Klotho.

The Osteogenic Differentiation of Human Dental Pulp Stem Cells through G0/G1 Arrest and the p-ERK/Runx-2 Pathway by Sonic Vibration.

Mechanical/physical stimulations modulate tissue metabolism, and this process involves multiple cellular mechanisms, including the secretion of growth factors and the activation of mechano-physically sensitive kinases. Cells and tissue can be modulated through specific vibration-induced changes in cell activity, which depend on the vibration frequency and occur via differential gene expression. However, there are few reports about the effects of medium-magnitude (1.12 g) sonic vibration on the osteogenic differentiation of human dental pulp stem cells (HDPSCs). In this study, we investigated whether medium-magnitude (1.12 g) sonic vibration with a frequency of 30, 45, or 100 Hz could affect the osteogenic differentiation of HDPSCs. Their cell morphology changed to a cuboidal shape at 45 Hz and 100 Hz, but the cells in the other groups were elongated. FACS analysis showed decreased CD 73, CD 90, and CD 105 expression at 45 Hz and 100 Hz. Additionally, the proportions of cells in the G0/G1 phase in the control, 30 Hz, 45 Hz, and 100 Hz groups after vibration were 60.7%, 65.9%, 68.3%, and 66.7%, respectively. The mRNA levels of osteogenic-specific markers, including osteonectin, osteocalcin, BMP-2, ALP, and Runx-2, increased at 45 and 100 Hz, and the ALP and calcium content was elevated in the vibration groups compared with those in the control. Additionally, the western blotting results showed that p-ERK, BSP, osteoprotegerin, and osteonectin proteins were upregulated at 45 Hz compared with the other groups. The vibration groups showed higher ALP and calcium content than the control. Vibration, especially at 100 Hz, increased the number of calcified nodes relative to the control group, as evidenced by von Kossa staining. Immunohistochemical staining demonstrated that type I and III collagen, osteonectin, and osteopontin were upregulated at 45 Hz and 100 Hz. These results suggest that medium magnitude vibration at 45 Hz induces the G0/G1 arrest of HDPSCs through the p-ERK/Runx-2 pathway and can serve as a potent stimulator of differentiation and extracellular matrix production.

The Histone Deacetylase Inhibitor (MS-275) Promotes Differentiation of Human Dental Pulp Stem Cells into Odontoblast-Like Cells Independent of the MAPK Signaling System.

The role of dental pulp stem cells (DPSCs) in dental tissue regeneration is gaining attention because DPSCs can differentiate into odontoblasts and other specialized cell types. Epigenetic modification has been found to play an important role in cell differentiation and regulation, among which histone deacetylase (HDAC) is involved in suppressing genes by removing histone acetyl groups. The use of HDAC inhibitor to control this is increasing and has been widely studied by many researchers. This study aimed to induce differentiation by causing epigenetic changes in odontoblast-related genes and the MAPK signaling pathway in human dental pulp stem cells. Western blot and immunofluorescence staining showed increased expression of DMP-1, ALP, DSPP, and RUNX2 compared to the control. However, activation of the MAPK signaling system was similar to but slightly different from the expression of odontoblast-related proteins. After 3 days, as shown by MTT and LDH assays, proliferation decreased overall, but cytotoxicity decreased at only a specific concentration. We confirmed that there was no change in mRNA expression of caspase 3 or 9 using real-time PCR. In addition, flow cytometry analysis confirmed that differentiation occurred due to the decrease in the expression of the CD73 and CD146. Although overall proliferation was reduced due to the G2/M inhibition of the cell cycle, the expression of BCL-2 protected the cells from cell death. Overall, cell proliferation decreased in response to MS-275, but it did not induce cytotoxicity in 5 nM and 10 nM concentration and induces differentiation into odontoblast-like cells.

Extremely Low-Frequency Electromagnetic Fields Increase the Expression of Anagen-Related Molecules in Human Dermal Papilla Cells via GSK-3ß/ERK/Akt Signaling Pathway.

Despite advances in medical treatments, the proportion of the population suffering from alopecia is increasing, thereby creating a need for new treatments to control hair loss and prevent balding. Human hair follicle dermal papilla cells (hDPCs), a type of specialized fibroblast in the hair bulb, play an essential role in controlling hair growth and in conditions like androgenic alopecia. This study aimed to evaluate the intensity-dependent effect of extremely low-frequency electromagnetic fields (ELF-EMFs) on the expression of anagen-related molecules in hDPCs in vitro. We examined the effect of ELF-EMF on hDPCs to determine whether activation of the GSK-3ß/ERK/Akt signaling pathway improved hDPC activation and proliferation; hDPCs were exposed to ELF-EMFs at a frequency of 70 Hz and at intensities ranging from 5 to 100 G, over four days. Various PEMF intensities significantly increased the expression of anagen-related molecules, including collagen IV, laminin, ALP, and versican. In particular, an intensity of 10 G is most potent for promoting the proliferation of hDPC and expression of anagen-related molecules. Moreover, 10 G ELF-EMF significantly increased ß-catenin and Wnt3α expression and GSK-3ß/ERK/Akt phosphorylation. Our results confirmed that ELF-EMFs enhance hDPC activation and proliferation via the GSK-3ß/ERK/Akt signaling pathway, suggesting a potential treatment strategy for alopecia.

Rice Bran Ash Mineral Extract Increases Pigmentation through the p-ERK Pathway in Zebrafish (Danio rerio).

The purpose of the present study is to evaluate the effect of rice bran ash mineral extract (RBM) on pigmentation in zebrafish (Danio rerio). Melanin has the ability to block ultraviolet (UV) radiation and scavenge free oxygen radicals, thus protecting the skin from their harmful effects. Agents that increase melanin synthesis in melanocytes may reduce the risk of photodamage and skin cancer. The present study investigates the effect of RBM on pigmentation in zebrafish and the underlying mechanism. RBM was found to significantly increase the expression of microphthalmia-associated transcription factor (MITF), a key transcription factor involved in melanin production. RBM also suppressed the phosphorylation of extracellular signal-regulated kinase (ERK), which negatively regulates zebrafish pigmentation. Together, these results suggest that RBM promotes melanin biosynthesis in zebrafish.

Synergistic effect of rice bran extract and extremely low-frequency electromagnetic fields on dermal papilla/melanocytes in melanogenesis.

Melanocytes in hair are located around dermal papilla cells at the tip of the hair follicle. In this study, we examined the melanogenesis of a three-dimensional (3D) hair dermal papilla model treated with natural extracts and electromagnetic fields (EMFs). The 3D model involved dermal papilla-like tissue (DPLT), an aggregation of a mixture of dermal papilla cells, and melanocytes in microwells. Rice bran extract (RBE), an EMF, and RBE/EMF were applied to different DPLT groups. The LDH assay indicated no cell stress in all experimental groups, and detection of tyrosinase activity demonstrated high activity in the RBE/EMF group. Western blot analysis of the RBE, EMF, and RBE/EMF groups revealed increased MITF, TRP-1, and tyrosinase expression. In addition, the mRNA expression of ET-1, laminin, bFGF, ß-catenin, MITF, and tyrosinase was increased in the RBE/EMF group, as demonstrated by RT-qPCR analysis. HMB45 and Fontana-Masson immunostaining showed that the RBE/EMF group had the highest melanin content. Therefore, RBE and EMF may be used as a material and therapy, respectively, for the treatment of vitiligo and white hair, through activation of melanogenesis in melanocytes. Bioelectromagnetics. 39:595-603, 2018. © 2018 The Authors. Bioelectromagnetics Published by Wiley Periodicals, Inc..

Pulsed Electromagnetic Fields Increase Pigmentation through the p-ERK/p-p38 Pathway in Zebrafish (Danio rerio).

Melanogenesis is a biological process resulting in the production of melanin pigment, which plays an important role in the prevention of sun-induced skin injury, and determines hair and skin color. So, a wide variety of approaches have been proposed to increase the synthesis of melanin. This study evaluated the effects of pulsed electromagnetic fields (PEMFs) on the pigmentation of zebrafish (Danio rerio) in vivo. We stimulated pigmentation in zebrafish by using specific frequencies and intensities of PEMFs. This study focuses on pigmentation using PEMFs, and finds that PEMFs, at an optimal intensity and frequency, upregulate pigmentation by the stimulated expression of tyrosinase-related protein 1 (TRP1), dopachrome tautomerase (DCT) through extracellular signal-regulated kinase(ERK) phosphorylation, and p38 phosphorylation signaling pathways in zebrafish. These results suggest that PEMFs, at an optimal intensity and frequency, are a useful tool in treating gray hair, with reduced melanin synthesis in the hair shaft or hypopigmentation-related skin disorders.

Local delivery of recombinant human FGF7 enhances bone formation in rat mandible defects.

Fibroblast growth factor 7 (FGF7) plays an important role in regulating the proliferation, migration, and differentiation of cells. However, the role of FGF7 in bone formation is not yet fully understood. We examined the effect of FGF7 on bone formation using a rat model of mandible defects. Rats underwent mandible defect surgery and then either scaffold treatment alone (control group) or FGF7-impregnated scaffold treatment (FGF7 group). Micro-CT and histological analyses revealed that the FGF7 group exhibited greater bone formation than did the control group 10 weeks after surgery. With the exception of total porosity (%), all bone parameters had higher values in the FGF7 group than in the control group at each follow-up after surgery. The FGF7 group showed greater expression of osteogenic markers, such as runt-related transcription factor 2, osterix, osteocalcin, bone morphogenetic protein 2, osteopontin, and type I collagen in newly formed bone than did the control group. The delivery of FGF7 also increased the messenger RNA expression of stromal-cell-derived factor 1 (SDF-1) and CXCR4 in newly formed bone in the FGF7 group compared with the control group. Further, addition of exogenous FGF7 induced migration of rat bone marrow stromal cells and increased the expression of SDF-1 and CXCR4 in the cells. Furthermore, the addition of FGF7 augmented mineralization in the cells with increased expression of osteogenic markers, and this augmentation was significantly suppressed by an inhibitor specific for c-Jun N-terminal kinase (SP600125) or extracellular-signal-regulated kinase (PD98059). Collectively, these results suggest that local delivery of FGF7 increases bone formation in a mandible defect with enhanced osteogenesis and chemoattraction.

Effects of Extremely Low Frequency Electromagnetic Fields on Melanogenesis through p-ERK and p-SAPK/JNK Pathways in Human Melanocytes.

This study evaluated frequency-dependent effects of extremely low frequency electromagnetic fields (ELF-EMFs) on melanogenesis by melanocytes in vitro. Melanocytes were exposed to 2 mT EMFs at 30-75 Hz for 3 days before melanogenesis was examined. Exposure to ELF-EMFs at 50 and 60 Hz induced melanogenic maturation without cell damage, without changing cell proliferation and mitochondrial activity. Melanin content and tyrosinase activity of cells exposed to 50 Hz were higher than in controls, and mRNA expression of tyrosinase-related protein-2 was elevated relative to controls at 50 Hz. Phosphorylated cyclic adenosine monophosphate response element-binding protein (p-CREB) levels were higher than controls in cells exposed to ELF-EMFs at 50-75 Hz. Immunohistochemical staining showed that melanocyte-specific markers (HMB45, Melan-A) were strongly expressed in cells exposed to EMFs at 50 and 60 Hz compared to controls. Thus, exposure to ELF-EMFs at 50 Hz could stimulate melanogenesis in melanocytes, through activation of p-CREB and p-p38 and inhibition of phosphorylated extracellular signal-regulated protein kinase and phosphorylated stress-activated protein kinase/c-Jun N-terminal kinase. The results may form the basis of an appropriate anti-gray hair treatment or be applied in a therapeutic device for inducing repigmentation in the skin of vitiligo patients.

Schwann-like cells differentiated from human dental pulp stem cells combined with a pulsed electromagnetic field can improve peripheral nerve regeneration.

The purpose of this study was to investigate the effect of Schwann-like cells combined with pulsed electromagnetic field (PEMF) on peripheral nerve regeneration. Schwann-like cells were derived from human dental pulp stem cells (hDPSCs) and verified with CD104, S100, glial fibrillary acidic protein (GFAP), laminin, and P75NTR immunocytochemistry. Gene expression of P75NTR and S100 were analyzed. Male Sprague-Dawley rats (200-250g, 6-week-old) were divided into seven groups (n = 10 each): control, sham, PEMF, hDPSCs, hDPSCs + PEMF, Schwann-like cells, Schwann-like cells + PEMF. Cells were transplanted (1 × 106 /10µl/rat) at crush-injury site or combined with PEMF (50 Hz, 1 h/day, 1 mT). Nerve regeneration was evaluated with functional test, histomorphometry and retrograde labelled neurons. Schwann-like cells expressed CD104, S100, GFAP, laminin, and p75 neurotrophin receptor (P75NTR ). P75NTR and S100 mRNA expression was highest in Schwann-like cells + PEMF group, which also showed increased Difference and Gap scores. Axons and retrograde labeled neurons increased in all treatment groups. Schwann-like cells, hDPSCs with or without PEMF, and PEMF only improved peripheral nerve regeneration. Schwann-like cells + PEMF showed highest regeneration ability; PEMF has additive effect on hDPSCs, Schwann-like cell in vitro and nerve regeneration ability after transplantation in vivo. Bioelectromagnetics. 37:163-174, 2016. © 2016 Wiley Periodicals, Inc.

Effects of electromagnetic field (PEMF) exposure at different frequency and duration on the peripheral nerve regeneration: in vitro and in vivo study.

PURPOSE: The purpose was to clarify the influence of frequency and exposure time of pulsed electromagnetic fields (PEMF) on the peripheral nerve regeneration. MATERIALS AND METHODS: Immortalized rat Schwann cells (iSCs) (1 × 10(2)/well) were exposed at four different conditions in 1 mT (50 Hz 1 h/d, 50 Hz 12 h/d, 150 Hz 1 h/d and 150 Hz 12h/d). Cell proliferation, mRNA expression of S100 and brain-derived neurotrophic factor (BDNF) were analyzed. Sprague-Dawley rats (200-250 g) were divided into six groups (n = 10 each): control, sham, 50 Hz 1 h/d, 50 Hz 12 h/d, 150 Hz 1 h/d and 150 Hz 12 Hr/d. Mental nerve was crush-injured and exposed at four different conditions in 1 mT (50 Hz 1 Hr/d, 50 Hz 12 Hr/d, 150 Hz 1 h/d and 150 Hz 12 h/d). Nerve regeneration was evaluated with functional test, histomorphometry and retrograde labeling of trigeminal ganglion. RESULTS: iSCs proliferation with 50 Hz, 1 h/d was increased from fourth to seventh day; mRNA expression of S100 and BDNF was significantly increased at the same condition from first week to third week (p < .05 vs. control); difference score was increased at the second and third week, and gap score was increased at the third under 50 Hz 1 h PEMF compared with control while other conditions showed no statistical meaning. Axon counts and retrograde labeled neurons were significantly increased under PEMF of four different conditions compared with control. Although there was no statistical difference, 50 Hz, 1 h PEMF showed highest regeneration ability than other conditions. CONCLUSION: PEMF enhanced peripheral nerve regeneration, and that it may be due to cell proliferation and increase in BDNF and S100 gene expression.

Co-treatment effect of pulsed electromagnetic field (PEMF) with human dental pulp stromal cells and FK506 on the regeneration of crush injured rat sciatic nerve.

PURPOSE: The purpose of this study was to determine whether crush injured rat sciatic nerve could be benefit from pulsed electromagnetic field (PEMF) combined with human dental pulp stromal cells (hDPSCs), with FK506 (Tacrolimus) for immune suppression and neuropromotion. MATERIALS AND METHODS: Male Sprague-Dawley rats (200-250 g, 6 week old) were distributed into 6 groups (n = 18 each): control, PEMF, FK506, PEMF + hDPSCs, PEMF + FK506, and PEMF + hDPSCs + FK506 groups. hDPSCs (cell = 1 × 106/10 µl/rat) were injected at the crush site immediate after injury. FK506 was administered 3 weeks in FK506 group (0.5 mg/kg/d) while pre-op 1 d and post-op 7 d in PEMF + FK506 and PEMF + hDPSCs + FK506 group; cell tracking was done with PKH26-labeled hDPSCs (cell = 1 × 106/10 µl/rat). The rats were follow-up for 3 weeks. RESULTS: PEMF + FK506 and PEMF + hDPSCs + FK506 group showed a sharp increase in sciatic function index (SFI), axon counts, densities, and labeled neurons in dorsal root ganglia (DRG) than control at 3 weeks. Other three treatment groups also showed higher axon counts, densities, and labeled neurons than control. Higher axon counts and densities were found in PEMF + FK506 and PEMF + hDPSCs + FK506 groups comparing with PEMF group. Brain-derived neurotrophic factor (BDNF) mRNA expression pattern in nerve segment and DRG was almost same. Higher expression level in all the treatment groups was discovered in the follow-up period, but there was no significant difference. CONCLUSIONS: All treatment groups can improve regeneration of neurons following crushed injury, PEMF + FK506 and PEMF + hDPSCs + FK506 groups showed higher regeneration ability than other three groups. FK506 plays an important role during hDPSCs transplantation.

Enhancing proliferation and ECM expression of human ACL fibroblasts by sonic vibration.

Effects of mechanical vibration on cell activity and behavior remain controversial: There has been evidence on both positive and negative effects. Furthermore, research on the anterior cruciate ligament (ACL) has as yet been limited and the frequency-related effects remain unknown, even though ACL injury is common and an injured ACL hardly spontaneously recovers. The object of this work was to address the influence of mechanical vibration on ACL fibroblasts, to determine the effects of frequencies, and to further study this effect at the cellular level. We found that sonic vibration affected ACL fibroblasts' proliferation and metabolism in a frequency-dependent manner, and 20 Hz gave rise to the most ACL cell activity and comprehensively increased extracellular matrix (ECM) contents, including collagen type I, collagen type III, fibronectin, elastin, tenascin, glycosaminoglycan (GAG), and the cytoskeleton protein vimentin. Thus, our results indicate that sonic vibration possesses frequency-dependent effects on proliferation and productivity of ACL fibroblast with an optimal frequency of 20 Hz under the present stimulation conditions, providing further information for future research in how vibrational stimulation manipulates ACL cellular behavior.

COMP-angiopoietin 1 increases proliferation, differentiation, and migration of stem-like cells through Tie-2-mediated activation of p38 MAPK and PI3K/Akt signal transduction pathways.

Recombinant COMP-Ang1, a chimera of angiopoietin-1 (Ang1) and a short coiled-coil domain of cartilage oligomeric matrix protein (COMP), is under consideration as a therapeutic agent capable of inducing the homing of cells with increased angiogenesis. However, the potentials of COMP-Ang1 to stimulate migration of mesenchymal stem cells (MSCs) and the associated mechanisms are not completely understood. We examined the potential of COMP-Ang1 on bone marrow (BM)-MSCs, human periodontal ligament stem cells (PDLSCs), and calvarial osteoblasts. COMP-Ang1 augmented Tie-2 induction at protein and mRNA levels and increased proliferation and expression of runt-related transcription factor 2 (Runx2), osterix, and CXCR4 in BMMSCs, but not in osteoblasts. The COMP-Ang1-mediated increases were inhibited by Tie-2 knockdown and by treating inhibitors of phosphoinositide 3-kinase (PI3K), LY294002, or p38 mitogen-activated protein kinase (MAPK), SB203580. Phosphorylation of p38 MAPK and Akt was prevented by siRNA-mediated silencing of Tie-2. COMP-Ang1 also induced in vitro migration of BMMSCs and PDLSCs. The induced migration was suppressed by Tie-2 knockdown and by CXCR4-specific peptide antagonist or LY294002, but not by SB203580. Furthermore, COMP-Ang1 stimulated the migration of PDLSCs into calvarial defect site of rats. Collectively, our results demonstrate that COMP-Ang1-stimulated proliferation, differentiation, and migration of progenitor cells may involve the Tie-2-mediated activation of p38 MAPK and PI3K/Akt pathways.

Comparison of light-emitting diode wavelength on activity and migration of rabbit ACL cells.

The purpose of this study was to evaluate the biological response and gene expression of New Zealand White Rabbit anterior cruciate ligament (ACL) fibroblasts for different wave lengths of light-emitting diode (LED) irradiation. In other words, this study was undertaken to evaluate the effects of different wavelengths of LED irradiation on cell growth, expression of extracellular matrix and growth factors, migration, and expression of actin and integrin. Proliferation assay showed that red (630 nm, 9.5 J/cm(2)) and green LED (530 nm, 9.8 J/cm(2)) irradiated cells were more increased than control group but there was no difference between the control group and the blue LED (460 nm, 27 J/cm(2)) irradiated group. Moreover, the expression of insulin-like growth factor, transforming growth factor-beta (TGF-ß1), and collagen I were significantly increased in the red and green LED-irradiated group, but the expression of collagen was decreased in the blue LED-irradiated group. The results of staining showed that collagen and TGF-ß1 were weaker in the control group and blue LED-irradiated cells, but stronger in the red and green LED-irradiated cells. Also, in the red and green LED-irradiated group, the expression of actin and integrin was not changed compared to the control group, but the expression of actin and integrin was decreased in the blue irradiated group. This study revealed that irradiation with a wavelength of 460 nm (blue LED) is cytotoxic to ACL cells, but irradiation with nontoxic fluencies of 530 (green LED) and 630 nm (red LED) wavelengths induced cell growth in cultured ACL cells.

Modulation of Inflammatory Responses to Enhance Nerve Recovery after Spinal Cord Injury.

Inflammation can occur at the wound site, and immune cells are necessary to trigger wound healing and tissue regeneration after injury. It is partly initiated by the rapid migration of immune cells such as neutrophils, inflammatory monocytes, and macrophages after spinal cord injury (SCI). Secondary inflammation can increase the wound area; thus, the function of tissues below the injury levels. Monocytes can differentiate into macrophages, and the macrophage phenotype can change from a pro-inflammatory phenotype to an anti-inflammatory phenotype. Therefore, various studies on immunomodulation have been performed to suppress secondary inflammation upon nerve damage. This editorial commentary focuses on various therapeutic methods that modulate inflammation and promote functional regeneration after SCI.

A novel strategy and characteristics of PVA/citric acid cross-linked hydrophilic elastic sponge of cellulose based on medicinal herb residue.

A new ultra-hydrophilic elastic sponge composite has been proposed. Medicinal herbs, commonly used in herbal medicine and subsequently discarded, are rich in natural polymer substances, making them promising candidates for various material industries. TEMPO-oxidized cellulose was extracted from medicinal herb residue, and the physicochemical properties of an ultra-hydrophilic elastic sponge, prepared through a PVA and CA impregnate cross-linking process, were investigated. The fabricated composite sponge exhibited an increase in compressive stress-strain proportional to the PVA cross-linking concentration, and its water retention capability was assessed through retention tests. Swelling tests for various solvents were conducted to evaluate the potential use of the sponge in diverse industries, revealing the highest swelling ratio in water. Pressure distribution measurements using prescale film indicated that the sponge's shock absorption capacity was enhanced by PVA cross-linking, leading to improved pressure dispersion.