• Molecules and Cells
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• 제40권3호
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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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• 제27권5호
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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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• 제46권4호
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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.

• Hip & pelvis
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• 제36권1호
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• pp.37-46
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• 2024

Purpose: The prognosis of total hip replacement (THR) after open reduction and internal fixation (ORIF) versus THR following non-operative treatment of acetabular fractures is unclear. Few studies have been conducted in this regard. Therefore, the purpose of the current study was to perform an assessment and compare the functional outcomes for study subjects in the ORIF and non-ORIF groups during the follow-up period compared to baseline. Materials and Methods: This longitudinal comparative study, which included 40 patients who underwent THR for either posttraumatic arthritis after fixation of an acetabular fracture or arthritis following conservative management of a fracture, was conducted for 60 months. Twenty-four patients had undergone ORIF, and 16 patients had undergone nonoperative/conservative management for acetabular fractures. Following THR, the patients were followed up for monitoring of functional outcomes for the Harris hip score (HHS) and comparison between the ORIF and non-ORIF groups was performed. Results: The HHS showed significant improvement in both ORIF and non-ORIF groups. At the end of the mean follow-up period, no significant variation in scores was observed between the groups, i.e., ORIF group (91.61±6.64) compared to non-ORIF group (85.74±11.56). A significantly higher number of re-interventions were required for medial wall fractures and combined fractures compared to posterior fractures (P <0.05). Conclusion: THR resulted in improved functional outcome during follow-up in both the groups; however, the ORIF group was observed to have better functional outcome. Re-intervention was not required for any of the posterior fractures at the end of the mean follow-up period.

• Clinics in Shoulder and Elbow
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• 제27권2호
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• pp.160-168
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• 2024

Background: Recurrent anterior shoulder dislocation (RASD) in cases of seizure disorders (SDs) total 50%-80% of all SD-associated shoulder instabilities. Based on the extent of bone loss, treatment options include bony and soft-tissue reconstructions, arthroplasty, and arthrodesis. The primary objective of this paper was to review the treatment options for RASD in SDs. Methods: Several bibliographic databases were searched for RASD treatment options in SD patients. The demographic outcome measures, the failure rate (defined as the relative risk of recurrence of dislocation postoperation), and the postoperative seizure recurrence rate were recorded. Results: We pooled 171 cases (187 shoulders) from 11 studies. Of these, one, five, two, two, and one reports studied Bankart's operation with remplissage (27 cases/29 shoulders), the Latarjet procedure (106/118), bone block operation (21/23), arthroplasty (11/11), and arthrodesis (6/6), respectively, in treating SD-associated RASD. The relative risk of failure between SD and non-SD patients was 3.76 (1.36-10.38) after the Latarjet operation. The failure rates were 17% and 13% for Bankart's operation with remplissage and the Latarjet procedure in SD patients, respectively, but 0% each for bone block operation, arthroplasty, and arthrodesis. The total rate of seizure recurrence after operation was 33% of the pooled cases. Conclusions: SD recurrence in the postoperative period, the size of the bone block, and the muscular attachments to a small coracoid autograft are the determinants of failure among various reconstructive operations in SD-associated RASD.

• Clinics in Shoulder and Elbow
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• 제27권2호
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• pp.169-175
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• 2024

Background: Incidental findings are commonly noted in advanced imaging studies. Few data exist regarding the rate of incidental findings on computed tomography (CT) for preoperative shoulder arthroplasty planning. This study aims to identify the incidence of these findings and the rate at which they warrant further work-up to help guide orthopedic surgeons in counseling patients. Methods: A retrospective review was performed to identify patients with available preoperative shoulder CT who subsequently underwent shoulder arthroplasty procedures at a single institution between 2015 and 2021. Data including age, sex, and smoking status were obtained. Radiology reports for CTs were reviewed for incidental findings and categorized based on location, tissue type, and/or body system. The rate of incidental findings and the rate at which further follow-up was recommended by the radiologist were determined. Results: A total of 617 patients was identified. There were 173 incidental findings noted in 146 of these patients (23.7%). Findings ranged from pulmonary (59%), skin/soft tissue (16%), thyroid (13%), vascular (9%), spinal (2%), and abdominal (1%) areas. Of the pulmonary findings, 50% were pulmonary nodules and 47% were granulomatous disease. Overall, the final radiology report recommended further follow-up for 50% of the patients with incidental findings. Conclusions: Incidental findings are relatively common in preoperative CTs obtained for shoulder arthroplasty, occurring in nearly one-quarter of patients. Most of these findings are pulmonary in nature. Overall, half of the patients with incidental findings were recommended for further follow-up. These results establish population data to guide orthopedic surgeons in patient counseling. Level of evidence: III.

• Molecules and Cells
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• 제41권6호
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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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• 제50권11호
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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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• 제14권6호
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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.

• 대한의용생체공학회:의공학회지
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• 제26권5호
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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.