• The Korean Journal of Oral and Maxillofacial Pathology
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• v.42 no.5
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• pp.145-152
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• 2018

A 57 years old female complained of severe pain on the right temporomandibular joint (TMJ) area. Her right condyle had been partly resected under surgical operation 13 years ago due to condyle hypertrophy, thereafter she felt dull pain on TMJ area and recently the lesion became severely swelled and painful leading to cancer phobia. The present radiological views showed slightly enlarged and sclerosed condyle with increased radiopacity, but its articular sliding function was almost disable during mouth opening. The patient's TMJ lesion was carefully managed with conservative physiotherapy and pain treatment. The microsection of condyle head obtained from the previous operation was re-evaluated histologically, and it was finally diagnosed as osteochondrosis dissecans (OCD), exhibiting hyperplastic proliferation of cartilage in condyle head and marked vascular dilatation in epiphyseal zone. This abnormal cartilage tissue was distinguishable from normal cartilage tissue found in the peripheral cartilaginous cap of the same microsection. The involved cartilage cap showed thick hypertrophic chondrocyte zone with horizontal and vertical clefts accompanying diffuse hyaline degeneration. The superficial fibrous zone of cartilage cap was thickened and frequently peeled off, while lower hypertrophic zone of cartilage cap was highly cellular and proliferative. Consequently, the endochondral ossification became aberrant and resulted pre-mature apoptosis of many hypertrophic chondrocytes, followed by diffuse and mild inflammatory reaction in the underlying marrow tissue. Therefore, it was suggested that this hypertrophic condyle lesion, OCD, be differentiated depending on radiological and histological features from ordinary condyle hyperplasia, osteochondroma, and osteoarthritis, and that the pathological confirmation of OCD may provide a reliable modality for dental and medical treatment of chronic and painful TMJ lesion.

• Journal of the Korean Society of Food Science and Nutrition
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• v.45 no.5
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• pp.634-641
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• 2016

The objective of this research was to investigate the in vivo effects of treatment with mulberry extract complex (MEC) on cartilage degeneration and pain severity in an experimental model of rat degenerative arthritis. Monosodium iodoacetate ($2mg/50{\mu}L$) was injected into right knee joints of rats, followed by administration of MEC for 8 weeks at 400 mg/kg or 800 mg/kg of body weight. The experimental data show that treatment with MEC inhibited degradation of glycosaminoglycan and collagen in cartilage. On the other hand, concentrations of cartilage oligomeric matrix protein, C-terminal telopeptide-2, matrix metalloproteinase (MMP)-2, MMP-9, and MMP-13 in serum decreased in comparison with the control. The MEC at all dose levels could inhibit formation of xylene-induced ear edema. In this study, MEC demonstrated significant anti-arthritis activity, which is required for improvement of degenerative arthritis. Based on these results, MEC may be employed for the development of new health foods to ease symptoms of degenerative arthritis.

• Journal of Veterinary Clinics
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• v.17 no.1
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• pp.76-82
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• 2000

This study was undertaken to find out the effect of persimmon leaves on histopathological changes of cadmium toxicity in mice. Seventy two BALB/c mice of male were divided into a control group(A) and five experimental groups (B, C, D, E, F) : group A received tap water and basal diet, group B received tap water and diet supplemented with 3% persimmon leaves alone, group C received basal diet and 300 ppm cadmium, group D, E and F received basal diet supplemented with 1, 3% and 7% persimmon leaves and 300 ppm cadmium respectively. Cadmium dissolved in tap water was used, and the persimmon leaves were mixed with feed. All mice were dissected on the 84th day. Pathological changes in liver, kidney, cortical osseous tissue of femoral shaft, bone trabecular of femur, and epiphyseal cartilage plate of femur were observed. Group B showed no significant changes as the control group. But group C showed the unclearness of specific cells in liver, the loss of architecture and necrosis of hepatocyte, degeneration and necrosis of renal convoluted tubules, desquamation and vacuolization of the greater part of the renal tubular epithelium, marked thinning of the cortical osseous tissue in femoral shaft, reduction of cancellous bone volume and decreaswe of trabecular number, and marked thinning of epiphyseal cartilage plate in femur. On the other hand, persimmon leaves-treated group showed a little convalescent changes an maintained their normal architectures in liver, kidney, cortical osseous tissue of femoral shaft, bone trabecular of femur, and epiphyseal cartilage plate of femur.

• Journal of Life Science
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• v.29 no.8
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• pp.888-894
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• 2019

Cartilage diseases, such as rheumatoid arthritis (RA) and osteoarthritis (OA), are associated with the loss of chondrocytes and degradation of articular cartilage. Recent studies revealed that inflammatory reactive oxygen species (ROS) and age-related oxidative stress can affect chondrocyte activity and cartilage homeostasis. We investigated changes in the levels of intracellular antioxidants during cellular senescence of primary chondrocytes from rat articular cartilages. Cellular senescence was induced by serial subculture (passages 0, 2, 4, and 8) of chondrocytes and measured using specific senescence-associated ${\beta}$-galactosidase ($SA-{\beta}-gal$) staining. ROS production increased significantly in the senescent chondrocytes. In addition, total glutathione (GSSG/GSH) and superoxide dismutase (SOD) levels and heme oxygenase-1 (HO-1) expression increased in senescent chondrocytes induced by serial subculture. Analysis of changes in intracellular antioxidant levels in articular cartilage from rats of different ages (5, 25, 40, and 72 wk) revealed that total glutathione levels were highest after 40 wk and slightly decreased after 72 wk as compared with those after 25 wk. SOD and HO-1 expression levels increased in accordance with age. Based on these results, we conclude that intracellular antioxidants may be associated with cartilage protection against excessive oxidative stress in the process of chondrocyte senescence and age-related cartilage degeneration in an animal model.

• Journal of Veterinary Science
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• v.24 no.6
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• pp.83.1-83.12
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• 2023

Background: Ellipticine (Ellip.) was recently reported to have beneficial effects on the differentiation of adipose-derived stem cells into mature chondrocyte-like cells. On the other hand, no practical results have been derived from the transplantation of bone marrow stem cells (BMSCs) in a rabbit osteoarthritis (OA) model. Objectives: This study examined whether autologous BMSCs incubated with ellipticine (Ellip.+BMSCs) could regenerate articular cartilage in rabbit OA, a model similar to degenerative arthritis in human beings. Methods: A portion of rabbit articular cartilage was surgically removed, and Ellip.+BMSCs were transplanted into the lesion area. After two and four weeks of treatment, the serum levels of proinflammatory cytokines, i.e., tumor necrosis factor α (TNF-α) and prostaglandin E2 (PGE2), were analyzed, while macroscopic and micro-computed tomography (CT) evaluations were conducted to determine the intensity of cartilage degeneration. Furthermore, immuno-blotting was performed to evaluate the mitogen-activated protein kinases, PI3K/Akt, and nuclear factor-κB (NF-κB) signaling in rabbit OA models. Histological staining was used to confirm the change in the pattern of collagen and proteoglycan in the articular cartilage matrix. Results: The transplantation of Ellip.+BMSCs elicited a chondroprotective effect by reducing the inflammatory factors (TNF-α, PGE2) in a time-dependent manner. Macroscopic observations, micro-CT, and histological staining revealed articular cartilage regeneration with the downregulation of matrix-metallo proteinases (MMPs), preventing articular cartilage degradation. Furthermore, histological observations confirmed a significant boost in the production of chondrocytes, collagen, and proteoglycan compared to the control group. Western blotting data revealed the downregulation of the p38, PI3K-Akt, and NF-κB inflammatory pathways to attenuate inflammation. Conclusions: The transplantation of Ellip.+BMSCs normalized the OA condition by boosting the recovery of degenerated articular cartilage and inhibiting the catabolic signaling pathway.

• Analytical Science and Technology
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• v.28 no.4
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• pp.260-269
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• 2015

The protective effects of extract powder of Angelica gigas on the degeneration of the articular cartilage in rats was investigated with monosodium iodoacetate (MIA)-induced osteoarthritis, The treatment of high concentration (50 μg/mL) of Angelica gigas effectively inhibited nitric oxide (NO) production induced by interleukin-1α (IL-1α) without any cytotoxicity. Specifically, mRNA and protein expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) were dose dependently reduced by extract powder of Angelica gigas. Importantly, mRNA expression in articular cartilage of inflammatory cytokines, tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6) were clearly reduced. The inflammatory cytokines in blood were also reduced as well. These results suggested that the protective effects on the degeneration of the articular cartilage was derived from the inhibitory effects of mRNA and protein expression of tested inflammatory cytokines which is linked to prevent the degradation of proteoglycan (PG), the main matrix content in articular cartilage. Meanwhile, the 2 hrs incubation of decursin, a major compound of extract powder in rat whole blood rapidely converted decursin into decursinol which shows string anti-inflammatory activity. The coverted decursinol was detected after 8 hrs in whole blood by LC-MS/MS. Conclusively, the inhibitory effects of inflammatory cytokines production in osteoarthritis may be derived from the production of decursinol, which performs against inflammatroy cytokines like TNF-α, IL-1β, and IL-6.

• Journal of Veterinary Clinics
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• v.18 no.2
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• pp.116-123
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• 2001

This study was undertaken to find out the effect of Korean safflower seed powder on histopathological changes of cadmium toxicity in mice. Fifty BALB/c mice were divided into a control group(A) and four experimental groups(B, C, D, E) : group A received tap water and basal diet, group B received tap water and diet supplemented with 3% Korean safflower seed powder alone, group C received basal diet and 300 $\mu\textrm{g}$/g of cadmium, group D and E received basal diet supplemented with 3% and 10% Korean safflower seed powder and 300$\mu\textrm{g}$/g of cadmium respectively. Cadmium dissolved in tap water was used, and the Korean safflower seed powder were mixed with feed. All mice were dissected on the 56th day. Histopathological changes in liver, kidney, lung, cortical osseous tissue of femoral shaft, bone trabecular of femur, and epiphyseal cartilage plate of femur were observed. Group B showed no significant changes compared with the control group. But group C showed the unclearness of specific cells in liver, the loss of architecture and focal necrosis of hepatocyte, the glomerular swelling, degeneration and necrosis of convoluted tubules, desquamation and vacuolization of the greater part of the renal tubular epithelium, the marked congestion and thickness of the wall of alveolus in lung, slightly thinning of the cortical osseous tissue in femoral shaft, reduction of cancellous bone volume and marked narrowness of bone trabecular, marked thinning of epiphyseal cartilage plate and irregular arrangement of columnar structure of cartilage cells. On the other hand, Korean safflower seed powder-treated group showed a little convalescent changes and maintained their normal architectures in liner, kidney, lung, cortical osseous tissue of femoral shaft, bone trabecular of femur and epiphyseal cartilage plate of femur.

• Journal of Korean Medicine Rehabilitation
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• v.33 no.3
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• pp.17-32
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• 2023

Objectives The purpose of this study was to investigate the antioxidant, anti-inflammatory and cartilage regeneration effects of Euiiin-tang water extract (EIIT) in the treatment of monosodium iodoacetate (MIA)-induced osteoarthritis in rats. Methods Animal models were divided into five groups. The normal group didn't do any treatments causing osteoarthritis. The control group was orally administerd distilled water instead of the drug, the positive control group used indomethacin 5 mg/kg, the EIIT 100 group used EIIT 100 mg/kg and the EIIT 200 group used EIIT 200 mg/kg, and seven rats were placed per group. We administered drug to rats for 2 weeks and analyzed oxidative stress-related proteins in joint tissue. Inflammation mediators and inflammatory cytokines induced by the activity of inflammation-related proteins were analyzed. In addition, the expression of anti-inflammatory cytokines and collagen-related factors were analyzed, and H&E staining and Safranin-O staining were performed to see the effect on histopathological changes. Results 1) Oxidative stress-related proteins were significantly reduced. 2) Inflammationrelated proteins, inflammatory mediators and inflammatory cytokines were significantly reduced. 3) Anti-inflammatory cytokines were significantly increased. 4) Collagen proteolysis factors significantly decreased, and collagen degradation inhibitory factor was significantly increased. 5) EIIT administration significantly reduced cartilage degeneration and deformation in H&E staining, and reduced proteoglycan destruction in Safranin-O staining. Conclusions From the above experimental results, it judges that Euiiin-tang has antioxidant, anti-inflammatory, and cartilage regeneration effects on osteoarthritis in rats induced by MIA.

• Maxillofacial Plastic and Reconstructive Surgery
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• v.28 no.5
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• pp.404-416
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• 2006

Purpose : This study was to clarify the changes in mandibular condyle after unilateral mandibular distraction osteogenesis throughout histological changes and expression of matrix metalloproteinase-2 (MMP-2) and tissue inhibitor of matrix metalloproteinase-2 (TIMP-2). Materials & Methods : Intraoral distractors were placed via submandibular incision in 8 dogs. Two unoperated animals served as controls. Distraction was performed five days after osteotomy as a rate of 0.5 mm twice per day for 10 days. Two animals were sacrificed on 7, 14, 28, and 56 days after completion of distraction, respectively. Ipsilateral condyles were harvested and processed for histological and immunohistochemical examinations. Results : The condyle cartilage is separated into four layers: fibrous layer, proliferative layer, hypertrophic layer, and calcified layer. At 7 days and 14 days after distraction, the condylar cartilage showed the decreased thickness of the articular cartilage and reduced cellularity. At 28 days after distraction, there was an increase in cellularity of fibrous, proliferative, and hypertrophic layer. However, it demonstrated reduced cellularity compared to the control. At 56 days of after distraction, the articular cartilage was an almost normal histologic structure. Positive Safranin-O staining, indicative of sulfated proteoglycans, was examined in the condylar cartilge of nonloaded control. At 7 days and 14 days after distraction, the sulfated proteoglycans is almost completely depleted from the noncalcified part of the condylar cartilage. At 28 days after distraction, there was an increase in Safranin-O staining intensity. However, the staining intensity of the experimental condyle was weaker than that of the control. At 56 days of after distraction, the condylar cartilage showed almost normal Safranin-O staining pattern. In control condyle, MMP-2 immunostaining was seen in fibrous, proliferative, and hypertrophic layer of condylar cartilage, however, it demonstrated lack of staining in fibrous and proliferative layer. At 7 days and 14 days after distraction, strong MMP-2 immunoreactivity was seen in the fibrous, proliferative and hypertrophic layer of the condylar cartilage. At 28 days after distraction, MMP-2 immunostaining was seen in the fibrous and hypertrophic layer of condylar cartilage, however, their immunoactivity was reduced. At 56 days after distraction, MMP-2 immunoreactivity showed almost normal immunostaining pattern. In control condyle, TIMP-2 immunostaining was primarily seen in fibrous and hypertrophic layer of condylar cartilage, however, it demonstrated lack of staining in proliferative layer. At 7 days after distraction, very weak TIMP-2 immunoreactivity appeared in fibrous, proliferative and hypertrophic layer of the condylar cartilage. At 14 days after distraction, weak TIMP-2 immunoreactivity was seen in the fibrous, proliferative and hypertrophic layer of the condylar cartilage. At 28 days after distraction, TIMP-2 immunoreactivity was increased in the fibrous and hypertrophic layer of condylar cartilage. At 56 days after completion of distraction, TIMP-2 immunoreactivity showed almost normal immunostaining pattern. Conclusions : The results show that short-term outcome of physiologic distraction osteogenesis may lead to degenerative changes in the condylar cartilage. These alterations in the condylar cartilage may be considered as a pressure-related degeneration of the cartilage tissue. However, the long-term results suggest that the condylar cartilage display repair activity after mandibular distraction osteogenesis.

• Applied Microscopy
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• v.31 no.3
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• pp.287-305
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• 2001

To investigate a role of cartilage canals in osteogenesis and growth of the vertebrae, in human fetuses ranging from 50 mm to 260 mm crown rump length were studied by electron microscopy. The initial appearance of cartilage canals of the vertebral body was observed at 60 mm fetus. In 80 mm fetus, primary ossification center in the vertebral body was first noted. The vertebral body showed calcified chondrocytes surrounded by a tone of hypertrophied chondrocytes and deep canals which terminated in calcified matrix. Most hypertrophied chondrocytes in the centrum showed in various stage of degeneration in disorderly arrangement. At the blind end of deep canal, osteogenic cells, osteoblasts and chondroclasts were observed. Resorption of unmineralized cartilage septa was undertaken by perivascular cells within cartilage canals. The ruffled border of the chondroclast was restricted to resorption site of calcified cartilagenous matrix. The periosteal bone formation was followed by the appearance of primary center of the centrum at 120 mm fetus. The osteoblasts of the perichondrium started to lay down a thin membranous bony lamella on the outer surface of the osseous trabeculae of the centrum. The processes of bone formation in the vertebral bodies were found to possess morphological similarities to that occurring at secondary center of the epiphysis of a long bone. These results indicate that the connective tissue cells within the cartilage canals proliferate and differentiate into osteoblasts at the site of endochondral ossification of the vertebrae.