• Molecules and Cells
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• v.40 no.3
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• pp.211-221
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• 2017

Transforming growth factor ${\beta}1$ $(TGF{\beta}1)/Smad4$ signaling plays a pivotal role in maintenance of the dynamic balance between bone formation and resorption. The microRNA miR-155 has been reported to exert a significant role in the differentiation of macrophage and dendritic cells. The goal of this study was to determine whether miR-155 regulates osteoclast differentiation through $TGF{\beta}1/Smad4$ signaling. Here, we present that $TGF{\beta}1$ elevated miR-155 levels during osteoclast differentiation through the stimulation of M-CSF and RANKL. Additionally, we found that silencing Smad4 attenuated the upregulation of miR-155 induced by $TGF{\beta}1$. The results of luciferase reporter experiments and ChIP assays demonstrated that $TGF{\beta}1$ promoted the binding of Smad4 to the miR-155 promoter at a site located in 454 bp from the transcription start site in vivo, further verifying that miR-155 is a transcriptional target of the $TGF{\beta}1/Smad4$ pathway. Subsequently, TRAP staining and qRT-PCR analysis revealed that silencing Smad4 impaired the $TGF{\beta}1$-mediated inhibition on osteoclast differentiation. Finally, we found that miR-155 may target SOCS1 and MITF to suppress osteoclast differentiation. Taken together, we provide the first evidence that $TGF{\beta}1/Smad4$ signaling affects osteoclast differentiation by regulation of miR-155 expression and the use of miR-155 as a potential therapeutic target for osteoclast-related diseases shows great promise.

• The Korean Journal of Physiology and Pharmacology
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• v.27 no.5
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• pp.437-448
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• 2023

Diabetic ulcer is usually seen in people with uncontrolled blood sugar. Reportedly, many factors such as impaired glucose metabolism, and macrovascular and microvascular diseases caused angiogenesis disorders and delayed the healing of diabetic ulcers, thus affecting the body's metabolism, nutrition, and immune function. This study aimed to explore the effect of paeonol on skin wound healing in diabetic rats and the related mechanism. A rat model of diabetic ulcer was established. High glucose-treated mouse skin fibroblasts were co-cultured with M1 or M2-polarized macrophages treated with or without paeonol. H&E and Masson staining were used to reveal inflammatory cell infiltration and collagen deposition, respectively. Immunohistochemistry visualized the expression of Ki67, CD31, and vascular endothelial growth factor (VEGF). Western blot was used to detect interleukin (IL)-1β, tumor necrosis factor (TNF)-α, IL-4, IL-10, CD31, VEGFA, and collagen I/III. The expression of iNOS and arginase 1 was revealed by immunofluorescence staining. Paeonol treatment augmented collagen deposition and the expression of Ki67, CD31, VEGF, and macrophage M2 polarization markers (IL-4 and IL-10) and reduced wound area, inflammatory cell infiltration, and macrophage M1 polarization markers (IL-1β and TNF-α) in the ulcerated area. In vitro, paeonol treatment promoted M2-polarization and repressed M1-polarization in macrophages, thereby improving the repair of cell damage induced by high glucose. Paeonol accelerates the healing of diabetic ulcers by promoting M2 macrophage polarization and inhibiting M1 macrophage polarization.

• Molecules and Cells
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• v.46 no.4
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• pp.231-244
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• 2023

Leucine-rich repeat containing 15 (LRRC15) has been identified as a contributing factor for cartilage damage in osteoarthritis; however, its involvement in rheumatoid arthritis (RA) and the underlying mechanisms have not been well characterized. The purpose of this study was to explore the function of LRRC15 in RA-associated fibroblast-like synoviocytes (RA-FLS) and in mice with collagen-induced arthritis (CIA) and to dissect the epigenetic mechanisms involved. LRRC15 was overexpressed in the synovial tissues of patients with RA, and LRRC15 overexpression was associated with increased proliferative, migratory, invasive, and angiogenic capacities of RA-FLS and accelerated release of pro-inflammatory cytokines. LRRC15 knockdown significantly inhibited synovial proliferation and reduced bone invasion and destruction in CIA mice. Runt-related transcription factor 1 (RUNX1) transcriptionally represses LRRC15 by binding to core-binding factor subunit beta (CBF-β). Overexpression of RUNX1 significantly inhibited the invasive phenotype of RA-FLS and suppressed the expression of proinflammatory cytokines. Conversely, the effects of RUNX1 were significantly reversed after overexpression of LRRC15 or inhibition of RUNX1-CBF-β interactions. Therefore, we demonstrated that RUNX1-mediated transcriptional repression of LRRC15 inhibited the development of RA, which may have therapeutic effects for RA patients.

• Molecules and Cells
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• v.41 no.6
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• pp.523-531
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• 2018

Tumour metastasis is one of the most serious challenges of cancer as it is the major cause of mortality in patients with solid tumours, including osteosarcoma (OS). In this regard, anti-metastatic genes have potential for metastasis inhibition strategies. Recent evidence showed the importance of breast cancer metastasis suppressor 1 (BRMS1) in control of OS invasiveness, but the regulation of BRMS1 in OS remains largely unknown. Here, we used bioinformatics analyses to predict BRMS1-targeting microRNAs (miRNAs), and the functional binding of miRNAs to BRMS1 mRNA was evaluated using a dual luciferase reporter assay. Among all BRMS1-targeting miRNAs, only miR-151b, miR-7-5p and miR-3200-5p showed significant expression in OS specimens. Specifically, we found that only miR-3200-5p significantly inhibited protein translation of BRMS1 via pairing to the 3'-UTR of the BRMS1 mRNA. Moreover, we detected significantly lower BRMS1 and significantly higher miR-3200-5p in the OS specimens compared to the paired adjacent non-tumour bone tissues. Furthermore, BRMS1 and miR-3200-5p levels were inversely correlated to each other. Low BRMS1 was correlated with metastasis and poor patient survival. In vitro, overexpression of miR-3200-5p significantly decreased BRMS1 levels and promoted OS cell invasion and migration, while depletion of miR-3200-5p significantly increased BRMS1 levels and inhibited OS cell invasion and migration. Thus, our study revealed that miR-3200-5p may be a critical regulator of OS cell invasiveness.

• Experimental and Molecular Medicine
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• v.50 no.11
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• pp.3.1-3.11
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• 2018

This study aimed to verify the effects of estrogen on the onset and development of adolescent idiopathic scoliosis and the mechanisms associated with these effects by constructing a pubescent bipedal rat model. Experiments were conducted to investigate whether scoliosis progression was prevented by a Triptorelin treatment. One hundred twenty bipedal rats were divided into female, OVX (ovariectomy), OVX + E2, Triptorelin, sham, and male groups. According to a spinal radiographic analysis, the scoliosis rates and curve severity of the female and OVX + E2 groups were higher than those in the OVX, Triptorelin, and male groups. The measurements obtained from the sagittal plane of thoracic vertebrae CT confirmed a relatively slower growth of the anterior elements and a faster growth of the posterior elements between T11 and T13 in the female and OVX + E2 groups than in the OVX and Triptorelin groups. Histomorphometry and immunohistochemistry revealed a significantly longer hypertrophic zone of the vertebral cartilage growth plates that expressed more type X collagen and less type II collagen in the OVX and Triptorelin groups than in the female and OVX + E2 groups. Ki67 immunostaining confirmed an increase in the proliferation of vertebral growth plate chondrocytes in the OVX group compared with the female and OVX + E2 groups. In conclusion, estrogen obviously increased the incidence of scoliosis and curve severity in pubescent bipedal rats. The underlying mechanism may be a loss of coupling of the endochondral ossification between the anterior and posterior columns. Triptorelin decreased the incidence of scoliosis and curve magnitudes in bipedal female rats.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.6
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• pp.3681-3684
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• 2013

Deregulated miRNAs participate in osteosarcoma genesis. In this study, the expression of miRNA-218 in human osteosarcomas, adjacent normal tissues and Saos-2 human osteosarcoma cells was first assessed. Then the precise role of miRNA-218 in osteosarcoma cells was investigated. Upon transfection with a miR-218 expression vector, the proliferation of Saos-2 human osteosarcoma cells determined using the ATPlite assay was significantly suppressed, whilw migration of Saos-2 cells detected by wound healing and invasion determined using transwells were dramatically inhibited. Potential target genes of miR-218 were predicted and T-cell lymphoma invasion and metastasis 1 (TIAM1) and matrix metalloproteinase 2 (MMP2) and 9 (MMP9) were identified. This was confirmed by western blotting, which showed that miR-218 expression inhibited TIAM1, MMP2 and MMP9 protein expression. Collectively, these data suggest that miR-218 acts as a tumor suppressor in osteosarcomas by down-regulating TIAM1, MMP2 and MMP9 expression.

• Journal of Biomedical Engineering Research
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• v.26 no.5
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• pp.257-264
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• 2005

This paper proposes an ionic polymer metal composite (IPMC) based artificial muscle to be applicable to the Myoelectric hand prosthesis. The IPMC consists of a thin polymer membrane with metal electrodes plated chemically on both faces, and it is widely applying to the artificial muscle because it is driven by relatively low input voltage. The control commands for the IPMC-based artificial muscle is given by electromyographic (EMG) signals obtained from human forearm. By an intended contraction of the human flexor carpi ulnaris and extensor carpi ulnaris muscles, we investigated the actuation behavior of the IPMC-based artificial muscle. To obtain higher actuation force of the IPMC, the single layered as thick as $800[{\mu}m]$ or multi-layered IPMC of which each layer can be as thick as $178[{\mu}m]$ are prepared. As a result, the bending force was up to the maximum 12[gf] from 1[gf] by actuating the single layered IPMC with $178[{\mu}m]$, but the bending displacement was reduced to 6[mm] from 30[mm]. The experimental results using an implemented IPMC control system show a possibility and a usability of the bio-mimetic artificial muscle.

• Journal of Korean Neurosurgical Society
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• v.57 no.6
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• pp.478-483
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• 2015

We report two rare cases of spinal intraosseous schwannoma (SIS) with sustained myelopathy symptoms and provide an updated review regarding SIS in the literature. A 71-year-old man experienced right lumbocrural pain and gait disturbance accompanied with paresthesia and right leg weakness. Imaging examinations revealed a mass with lesions in L4 vertebral body causing bone destruction and spinal cord compression. Complete resection of the well-demarcated tumor and posterior fusion were performed. A 54-year-old female reported bilateral gait disturbance, paresthesia, and numbness without weakness, and imaging revealed a posterior mass from T9 causing spinal cord compression and bone erosion. The tumor was completely separated from the spinal nerve root. The tumors from both patients were confirmed as schwannomas. Tumor recurrence was not observed at the 2-4 year follow-up. Although rare, SIS should be considered during differential diagnosis and can affect treatment planning. SIS symptoms vary depending on tumor location, and fusion is frequently necessary for spinal reconstruction after complete tumor resection.

• Proceedings of the KOSOMBE Conference
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• v.1997 no.05
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• pp.253-256
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• 1997

KESF-1 foot conceptually provides storage of potential energy and is converted to kinetic energy throughout the weight - bearing phase of the gait cycle. This stored energy is progressively released as the foot continues through the toe-off phase to rebound and propel the body forward. A weight deflects the keel through a predetermined range, then the keel "springs back" as weight is removed. Foot designs criteria were selected to guide development beyond the proof-of concept composite material keels; 1) store and return energy (1-3/4 " metatarsal deflection at 435 pounds vertical load), 2) natural feel and stability; 3) useful life of 3-years: 4) lightweight; 5) reduced production costs. The purpose of this study is developed the comfortable stable foot that fitted with Korean lifestyle and road condition. The results produced the realistic cosmetic foot cover with polyurethane form and the keel composed with composite materials of both glass fiber and carbon fiber.

• 제어로봇시스템학회:학술대회논문집
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• 2005.06a
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• pp.1278-1282
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• 2005

Air mattress is now used widely to prevent the pressure ulcer by reducing the localized pressure peaks. In this paper an air-cell mattress and its pressure control method based on an approximate anthropometric model are presented. The air-cell mattress has eighteen cylindrical air cells made of porous material allowing air leakage to contribute in reducing the development of pressure ulcer by lowering the pressure peak, temperature and humidity. To determine an optimal air-cell pressure appropriate for each user, we divide the parts of the body into four sections such as head, trunk, hip, and leg. Then, the pressure of each section is independently calculated from the weight of each part based on the individual body height and weight and the approximate anthropometric model. Air supply system for the air-cell mattress is implemented by using four electronic solenoid valves and an air compressor, and it is driven by a real-time micro-controller. The experimental results with seven subjects shows that the proposed air-cell mattress is effective for the prevention of the pressure ulcer.