• Molecules and Cells
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• v.46 no.4
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• pp.245-255
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• 2023

This study aimed to exploring the pathophysiological mechanism of 7α,25-dihydroxycholesterol (7α,25-DHC) in osteoarthritis (OA) pathogenesis. 7α,25-DHC accelerated the proteoglycan loss in ex vivo organ-cultured articular cartilage explant. It was mediated by the decreasing extracellular matrix major components, including aggrecan and type II collagen, and the increasing expression and activation of degenerative enzymes, including matrix metalloproteinase (MMP)-3 and -13, in chondrocytes cultured with 7α,25-DHC. Furthermore, 7α,25-DHC promoted caspase-dependent chondrocyte death via extrinsic and intrinsic pathways of apoptosis. Moreover, 7α,25-DHC upregulated the expression of inflammatory factors, including inducible nitric oxide synthase, cyclooxygenase-2, nitric oxide, and prostaglandin E₂, via the production of reactive oxygen species via increase of oxidative stress in chondrocytes. In addition, 7α,25-DHC upregulated the expression of autophagy biomarkers, including beclin-1 and microtubule-associated protein 1A/1B-light chain 3 via the modulation of p53-Akt-mTOR axis in chondrocytes. The expression of CYP7B1, caspase-3, and beclin-1 was elevated in the degenerative articular cartilage of mouse knee joint with OA. Taken together, our findings suggest that 7α,25-DHC is a pathophysiological risk factor of OA pathogenesis that is mediated a chondrocyte death via oxiapoptophagy, which is a mixed mode of apoptosis, oxidative stress, and autophagy.

• Polymer(Korea)
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• v.36 no.3
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• pp.357-363
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• 2012

Surface-modified poly(L-lactic acid) (PLLA) films and scaffolds were treated with plasma discharge in oxygen gas and subsequently subjected to $in$ $situ$ grafting of acrylic acid (AA) in order to increase the cell compatibility. The surface of AA-grafted PLLA was converted to hydroxyapatite (HA)-deposited PLLA in stimulated body fluid (SBF). After the samples were immersed in phosphate-buffered saline (PBS), fetal bovine serum (FBS), normal saline, or cell medium, the water contact angles were significantly reduced on the surface of HA-deposited PLLA. Chondrocyte and osteoblast showed a higher attachment and cell proliferation on HA-deposited surfaces and in particular, it was confirmed that chondrocyte was considerably influenced by HA. However, osteoblast showed better cell proliferation on the surfaces immersed in FBS, cell medium or HA-deposited surface. In addition, the cell proliferation in 3D scaffolds was much higher than that on film type, irrespective of chondrocyte and osteoblast. Therefore, such surface-modified PLLAs are expected to be useful as organic-inorganic hybrid scaffolds in the regeneration of cartilage and bone.

• Proceedings of the Zoological Society Korea Conference
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• 2001.10a
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• pp.194.2-194
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• 2001

No Abstract, See Full Text

• 대한관절경학회:학술대회논문집
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• 2009.10a
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• pp.81-82
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• 2009

• The korean journal of orthodontics
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• v.13 no.2
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• pp.155-163
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• 1983

Many different appliances have been used to move teeth or to attempt to inhibit or stimulate growth of the jaws. Especially, Orthopedic force was used to apply a constant force on the mandible. Various orthopedic forces bring the changes of surrounding tissue, growth and development on the mandibular joint. Author carried out this study to find the histological changes of the mandibular joint in rats when the mandible applied posterior displacement. For the purpose of this study, $009\times036inch$ closed coil spring and 030inch orthopedic wire were used between the post occipital region and the chin region in order to render the orthopedic forces, posteriorly. The experimental animals vu. used 1 month old (GroupI), 3 months old (Group II), and 12 months old (Group III) rats. Following results were obtained; 1. At the beginning of the experimental Group I, there were predominant increment of Cartilage layer in the posterior parts of condylar head. Especially, the mature chondrocyte zone was increased. 2. In the experimental Group II, the chondroblastic zone was decreased while it showed slightly increased mature cartilage zone. 3. In the experimental Group III, the mature chondrocyte zone was disappeared gradually and there was a tendency to reduce the endochondral bone formation in condylar head. 4. After 30 days of experimental Group I and in experimental Group II, there was a tendency to decrease the immature cellular zone in the glenoid fossa by pressure. 5. There were no histological changes in the articular disc by pressure.

• Molecules and Cells
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• v.25 no.1
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• pp.1-6
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• 2008

Osteoarthritis (OA), one of the most common skeletal disorders characterized by cartilage degradation and osteophyte formation in joints, is induced by accumulated mechanical stress; however, little is known about the underlying molecular mechanism. Several experimental OA models in mice by producing instability in the knee joints have been developed to apply approaches from mouse genetics. Although proteinases like matrix metalloproteinases and aggrecanases have now been proven to be the principal initiators of OA progression, clinical trials of proteinase inhibitors have not been successful for the treatment, turning the interest of researchers to the upstream signals of proteinase induction. These signals include undegraded and fragmented matrix proteins like type II collagen or fibronection that affects chondrocytes through distinct receptors. Another signal is proinflammatory factors that are produced by chondrocytes and synovial cells; however, recent studies that used mouse OA models in knockout mice did not support that these factors have a role in the central contribution to OA development. Our mouse genetic approaches found that the induction of a transcriptional activator Runx2 in chondrocytes under mechanical stress contributes to the pathogenesis of OA through chondrocyte hypertrophy. In addition, chondrocyte apoptosis has recently been identified as being involved in OA progression. We hereby propose that these endochondral ossification signals may be important for the OA progression, suggesting that the related molecules can clinically be therapeutic targets of this disease.

• BMB Reports
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• v.45 no.5
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• pp.317-322
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• 2012

2-deoxy-D-glucose(2DG)-caused endoplasmic reticulum (ER) stress inhibits protein phosphorylation at tyrosine residues. However, the accurate regulatory mechanisms, which determine the inflammatory response of chondrocytes to ER stress via protein tyrosine phosphorylation, have not been systematically evaluated. Thus, in this study, we examined whether protein phosphorylation at tyrosine residues can modulate the expression and glycosylation of COX-2, which is reduced by 2DG-induced ER stress. We observed that protein tyrosine phosphatase (PTP) inhibitors, sodium orthovanadate (SOV), and phenylarsine oxide (PAO) significantly decreased expression of ER stress inducible proteins, glucose-regulated protein 94 (GRP94), and CCAAT/ enhancer-binding-protein- related gene (GADD153), which was induced by 2DG. In addition, we demonstrated that SOV and PAO noticeably restored the expression and glycosylation of COX-2 after treatment with 2DG. These results suggest that protein phosphorylation of tyrosine residues plays an important role in the regulation of expression and glycosylation during 2DG-induced ER stress in rabbit articular chondrocytes.

• Proceedings of the Korean Society of Precision Engineering Conference
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• 2006.05a
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• pp.173-174
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• 2006

Understanding chondrocyte behavior inside complex, three-dimensional environments with controlled patterning of geometrical factors would provide significant insights into the basic biology of tissue regenerations. One of the fundamental limitations in studying such behavior has been the inability to fabricate controlled 3D structures. To overcome this problem, we have developed a three-dimensional microfabrication system. This system allows fabrication of predesigned internal architectures and pore size by stacking up the photopolymerized materials. Photopolymer SL5180 was used as the material for 3D scaffolds. The results demonstrate that controllable and reproducible inner-architecture can be fabricated. Chondrocytes harvested from human nasal septum were cultured in two kinds of 3D scaffolds to observe cell adhesion behavior. Such 3D scaffolds might provide effective key factors to study cell behavior in complex environments and could eventually lead to optimum design of scaffolds in various tissue regenerations such as cartilage, bone, etc. in a near future.

• Journal of Physiology & Pathology in Korean Medicine
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• v.22 no.2
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• pp.390-396
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• 2008

Osteoarthritis(OA) diseases are characterized by joint pain, tenderness, limitation of movement, crepitus, occasional effusion, and variable degrees of inflammation without systemic effects. We investigated the effects of Achyrantis radixs cream treatment and low intensity ultrasound in monosodium iodoacetate(MIA) induced experimental osteoarthritis rat. Sprague-Dawley 40 rats of 7-8 weeks, weight $250\;{\pm}\;50$ g were divided into four groups including the control group and ostoarthritis group(30 rats). Histopathological examination, Mankin's score, and immunohistochemical were performed. Histological findings in control group that are similar to those observed in human osteoarthritis, such as disorganization of chondrocytes, erosion and fibrillation of cartilage surface, and subchondral bone exposure. Safranin O-fast green staining revealed that marked diffuse reduction of proteoglycans and chondrocyte treated with MIA. The Mankin's score were closely correlated to the grade of histological findings. The level of Bax and caspase-3 expression decreased experimental groups. This study shows that a Acyranthes Radix cream treatment and low intensity ultrasound exerts a beneficial influence on the severity of chondral lesion in osteoarthritis rats. This treatments could related to a reduced level of chondrocyte apoptosis through anti-apoptotoc capacities of MIA-induced apoptotic protein overexpression.

• Physical Therapy Rehabilitation Science
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• v.2 no.1
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• pp.21-26
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• 2013

Objective: The aim of this study was to investigate the effect of therapeutic ultrasound (US) of cell viability and inflammatory cytokine in rat articular chondrocyte cultures stimulated with lipopolysaccharide (LPS). Design: One group pretest-posttest design. Methods: Cultured chondrocytes were treated with US and/or LPS and assessed for viability, Tumor necrosis factor $(TNF)-{\alpha}$ and Interleukin (IL)-1 production. Results: Oxidative stress was induced in rat chondrocytes with LPS. The cell viability was decreased in chondrocytes after treatment with LPS. The viability revealed that low-intensity pulsed ultrasound (LIPUS) exerted no significant cytotoxicity in the rat chondrocyte. LIPUS inhibited decreased cell viability in the presence of LPS ($30{\mu}g/ml$) in a intensity dependent pattern at LIPUS (p<0.05). $TNF-{\alpha}$ production in the presence of LPS was also inhibited in a dose dependent manner (p<0.05 from $30mW/cm^2$). IL-1 production in the presence of LPS was inhibited as well (p<0.05 from $7.5mW/cm^2$). Conclusions: Our results demonstrate that US was the anti-inflammatory effect of chondrocytes. LIPUS may exert its anti inflammatory effects through inhibition of $TNF-{\alpha}$ and IL-1 synthesis. These results suggest that US have potential for use as a pain relief and reduce the articular destruction.