• Journal of Life Science
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• v.28 no.7
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• pp.874-883
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• 2018

Osteoporosis is a disease that increases the risk of fracture by decreasing the mass and strength of bone. It is caused by imbalance of osteoclast bone formation and osteoclast bone resorption. Bone formation by osteoblast is activated via bone morphogenetic proteins and runt-related transcription factor 2. $Wnt/{\beta}-catenin$ signaling and bone resorption by osteoclast are initiated by the binding of receptor activator of nuclear $factor-{\kappa}B$ ligand and receptor activator of nuclear $factor-{\kappa}B$. Menopausal women are at risk for many diseases due to hormonal imbalances, and osteoporosis is the most common metabolic disorder in 30% of postmenopausal women. When estrogen is deficient, bone resorption of osteoclasts is promoted, and the risk of osteoporosis especially increases in postmenopausal women. Hormone replacement therapy has been widely used to relieve or treat the symptoms of menopausal syndrome. However, long-term administration of hormone therapy has been associated with a high risk of side effects, such as breast cancer, ovarian cancer, and uterine cancer. Recently, phytochemicals have been actively studied as a phytoestrogen, which has an estrogen-like activity to cope with symptoms of menopausal syndrome. Therefore, in this review, we investigated the differentiation mechanism of osteoblast and osteoclast and the role of estrogen and phytoestrogen in bone metabolism in relation to previous studies.

• IMMUNE NETWORK
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• v.14 no.1
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• pp.45-53
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• 2014

Osteoarthritis (OA) is a degenerative joint disease characterized by a progressive loss of cartilage. And, increased oxidative stress plays a relevant role in the pathogenesis of OA. Ursodeoxycholic acid (UDCA) is a used drug for liver diseases known for its free radical-scavenging property. The objectives of this study were to investigate the in vivo effects of UDCA on pain severity and cartilage degeneration using an experimental OA model and to explore its mode of actions. OA was induced in rats by intra-articular injection of monosodium iodoacetate (MIA) to the knee. Oral administration UDCA was initiated on the day of MIA injection. Limb nociception was assessed by measuring the paw withdrawal latency and threshold. Samples were analyzed macroscopically and histologically. Immunohistochemistry was used to investigate the expression of interleukin-$1{\beta}$ (IL-$1{\beta}$), IL-6, nitrotyrosine and inducible nitric oxide synthase (iNOS) in knee joints. UDCA showed an antinociceptive property and attenuated cartilage degeneration. OA rats given oral UDCA significantly exhibited a decreased number of osteoclasts in subchondral bone legion compared with the vehicle-treated OA group. UDCA reduced the expression of IL-$1{\beta}$, IL-6, nitrotyrosine and iNOS in articular cartilage. UDCA treatment significantly attenuated the mRNA expression of matrix metalloproteinase-3 (MMP-3), -13, and ADAMTS5 in IL-$1{\beta}$-stimulated human OA chondrocytes. These results show the inhibitory effects of UDCA on pain production and cartilage degeneration in experimentally induced OA. The chondroprotective properties of UDCA were achieved by suppressing oxidative damage and inhibiting catabolic factors that are implicated in the pathogenesis of cartilage damage in OA.

• The korean journal of orthodontics
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• v.25 no.1 s.48
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• pp.101-110
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• 1995

The purpose of this study was to observe the tissue response to the orthodontic force applied immediately after buccal horizontal subapical osteotomy of maxilla. Five mongrel cats weighing about 2.5 Kg were used for this experiment. The left upper canine and premolar of each cat served as a experimental side and the right ones as a control side. On the experimental side, a 100gm orthodontic force was applied between the upper canine and premolar immediately after the osteotomy. On the control side, the same orthodontic force was applied without the osteotomy. After 7days, the experimental animals were sacrificed. The results were as follows: 1. In the pressure zones of the experimental group, significant increase of osteoclasts and direct resolution along the alveolar bone surface was observed as compared with those of the control group. 2. In the pressure 2ones of the experimental group, a less extensive hyalinized zone was observed than those of the control group. 3. In the pressure zones of both group, no root resorption was found. 4. Tn the tension zones of the experimental group, new bone deposition increased along the alveolar bone surface as compared with those of the control group. In conclusion, the results suggest the possibility that early orthodontic treatment after orthognathic surgery may have some benefits if the stability of the repositioned segment at surgery is secured.

• The korean journal of orthodontics
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• v.25 no.1 s.48
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• pp.31-42
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• 1995

This study was designed to evaluate the expression of growth factor in periodontal tissue during the experimental movement of rat incisors by LSAB(Labelled streptavidine Biotin) immunohistochemical staining for EGF(Epidermal growth factor). 23 Sprague-Dawley rats were divided into a control group(3rats) and experimental groups(20rats), where a force(75g) from helical springs across the maxillary incisors was applied. Experimental groups were sacrificed at 12 hours, 1, 4, 7 and 14 days, after force application, respectively. And Tissue slides of control and experimental groups were studied immunohistochemically and histologically. The results were as follows : 1. In 14days after force application, periodontal fibers were strectched on the tension side, and compressed In pressure side of all experimental groups, and the arrangement of periodontal fibers was not recovered yet. 2. The degree of EGF expression in control group was strongly positive in the oral epithelium, predentin, capillaries in pulp and periodontal spaces. But osteoblasts and osteoclasts were stained mildly positive. 3. EGF expression was mild and diffuse in 12 hours, 1, 4 and 7 days of experimental groups and was not significantly different between the tension and pressure sides. 4. The degree of EGF expression in the 14-day experimental group was higher than any other group. And the tension side showed a more positive EGF expression than the pressure side. The apical area revealed a more positive EGF expression than the cervical area.

• International Journal of Oral Biology
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• v.30 no.2
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• pp.47-57
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• 2005

Leptin, the product of the obese gene, is a circulating hormone secreted primarily from adipocytes. Several results suggest that leptin is important mediators of bone metabolism. The present study was undertaken to determine the effects of leptin on anti-osteoclastogenesis using murine precursors cultured on Ca-P coated plates and on the production of osteoprotegerin (OPG) in osteoblastic cells. Additionally, this study examined the possible involvement of prostaglandin $E_2\;(PGE_2)$/protein kinase C (PKC)-mediated signals on the effect of leptin on anti-osteoclastogenesis to various culture systems of osteoclast precursors. Osteoclast generation was determined by counting tartrate-resistant acid phosphatase positive [TRAP (+)] multinucleated cells (MNCs). Osteoclastic activity was determined by measuring area of resorption pits formed by osteoclasts on Ca-P coated plate. The number of 1,25-dihydroxycholecalciferol $(1,25[OH]_2D_3)$- or $PGE_2$-induced TRAP (+) MNCs in the mouse bone marrow cell culture decreased significantly after treatment with leptin. The number of receptor activator of NF-kB ligand (RANKL)-induced TRAP (+) MNCs in M-CSF dependent bone marrow macrophage (MDBM) cell or RAW264.7 cell culture decreased significantly with leptin treatment. Indomethacin inhibited osteoclast generation induced by $1,25[OH]_2D_3$ and dexamethasone, however, no significant differences were found in the leptin treated group when compared to the corresponding indomethacin group. Phorbol 12-myristate 13-acetate (PMA), a PKC activator, inhibited osteoclast generation induced by $1,25[OH]_2D_3$. The number of TRAP (+) MNCs decreased significantly with treatment by PMA at concentrations of 0.01 and $0.1{\mu}M$ in culture. Leptin inhibited PMA-mediated osteoclast generation. Isoquinoline-5-sulfonic 2-methyl-1-piperazide dihydrochloride (H7) had no effect on osteoclast generation induced by $1,25[OH]_2D_3$. Cell culture treatment with leptin resulted in no significant differences in osteoclast generation compared to the corresponding H7 group. Indomethacin showed no significant effect on TRAP (+) MNCs formation from the RAW264.7 cell line. PMA inhibited TRAP (+) MNCs formation induced by RANKL in the RAW264.7 cell culture. H7 had no effect on osteoclast generation from the RAW264.7 cell line. There was no difference compared with the corresponding control group after treatment with leptin. $1,25[OH]_2D_3$- or $PGE_2$-induced osteoclastic activity decreased significantly with leptin treatment at a concentration of 100 ng/ml in mouse bone marrow cell culture. Indomethacin, PMA, and H7 significantly inhibited osteoclastic activity induced by $1,25[OH]_2D_3$ in mouse bone marrow cell culture. No significant differences were found between the leptin treated group and the corresponding control group. The secretion of OPG, a substance known to inhibit osteoclast formation, was detected from the osteoblasts. Treatment by leptin resulted in significant increases in OPG secretion by osteoblastic cells. Taken these results, leptin may be an important regulatory cytokines within the bone marrow microenvironment.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.36 no.5
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• pp.341-345
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• 2010

Introduction: Skeletal homeostasis is normally maintained by the stability between bone formation by osteoblasts and bone resorption by osteoclasts. However, the correlation between the inflammatory reaction and osteoblastic differentiation of cultured osteoprogenitor cells has not been fully investigated. This study examined the effects of inflammatory cytokines on the osteoblastic differentiation of cultured human periosteal-derived cells. Materials and Methods: Periosteal-derived cells were obtained from the mandibular periosteum and introduced into the cell culture. After passage 3, the periosteal-derived cells were further cultured in an osteogenic induction Dulbecco's modified Eagle's medium (DMEM) medium containing dexamethasone, ascorbic acid, and $\beta$-glycerophosphate. In this culture medium, tumor necrosis factor (TNF)-$\alpha$ with different concentrations (0.1, 1, and 10 ng/mL) or interleukin (IL)-$1{\beta}$ with different concentrations (0.01, 0.1, and 1 ng/mL) were added. Results: Both TNF-$\alpha$ and IL-$1{\beta}$ stimulated alkaline phosphatase (ALP) expression in the periosteal-derived cells. TNF-$\alpha$ and IL-$1{\beta}$ increased the level of ALP expression in a dose-dependent manner. Both TNF-$\alpha$ and IL-$1{\beta}$ also increased the level of alizarin red S staining in a dose-dependent manner during osteoblastic differentiation of cultured human periosteal-derived cells. Conclusion: These results suggest that inflammatory cytokines TNF-$\alpha$ and IL-$1{\beta}$ can stimulate the osteoblastic activity of cultured human periosteal-derived cells.

• Nutrition Research and Practice
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• v.11 no.3
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• pp.190-197
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• 2017

BACKGROUND/OBJECTIVES: Gallus gallus domesticus (GD) is a natural mutant breed of chicken in Korea with an atypical characterization of melanin in its tissue. This study investigated the effects of melanin extracts of GD on osteoblast differentiation and inhibition of osteoclast formation. MATERIALS/METHODS: The effects of the melanin extract of GD on human osteoblast MG-63 cell differentiation were examined by evaluating cell viability, osteoblast differentiation, and expression of osteoblast-specific transcription factors such as bone morphogenetic protein 2 (BMP-2), small mothers against decapentaplegic homologs 5 (SMAD5), runt-related transcription factor 2 (RUNX2), osteocalcin and type 1 collagen (COL-1) by reverse transcription-polymerase chain reaction and western blotting analysis. We investigated the inhibitory effect of melanin on the osteoclasts formation through tartrate-resistant acid phosphatase (TRAP) activity and TRAP stains in Raw 264.7 cell. RESULTS: The melanin extract of GD was not cytotoxic to MG-63 cells at concentrations of $50-250{\mu}g/mL$. Alkaline phosphatase (ALP) activity and bone mineralization of melanin extract-treated cells increased in a dose-dependent manner from 50 to $250{\mu}g/mL$ and were 149% and 129% at $250{\mu}g/mL$ concentration, respectively (P < 0.05). The levels of BMP-2, osteocalcin, and COL-1 gene expression were significantly upregulated by 1.72-, 4.44-, and 2.12-fold in melanin-treated cells than in the control cells (P < 0.05). The levels of RUNX2 and SMAD5 proteins were higher in melanin-treated cells than in control vehicle-treated cells. The melanin extract attenuated the formation of receptor activator of nuclear factor kappa-B ligand-induced TRAP-positive multinucleated RAW 264.7 cells by 22%, and was 77% cytotoxic to RAW 264.7 macrophages at a concentration of $500{\mu}g/mL$. CONCLUSIONS: This study provides evidence that the melanin extract promoted osteoblast differentiation by activating BMP/SMADs/RUNX2 signaling and regulating transcription of osteogenic genes such as ALP, type I collagen, and osteocalcin. These results suggest that the effective osteoblastic differentiation induced by melanin extract from GD makes it potentially useful in maintaining bone health.

• Herbal Formula Science
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• v.22 no.1
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• pp.151-165
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• 2014

Objectives : The aim of this study was to evaluate the efficacy of Aconiti Lateralis Preparata Radix (AP) and Acanthopanacis Cortex (AT) extracts in bone-derived adipocyte OP9 cell, osteoclast and osteoblast-like MG63 cells. Methods : MTT assay was used to evaluate the cytotoxicity of AP and AT extracts on OP9, osteoclast and MG63 cells. OP9 cells were treated with AP and AT, and the alterations in fat storage in the cells were determined by the Oil red O. To explain effects of RANKL-induced osteoclast differentiation in bone marrow macrophages, we performed the TRAP staining. The protein level of CAAAT/enhancer binding protein alpha ($C/EBP{\alpha}$) and peroxisome proliferator-activated receptor ${\gamma}$ ($PPAR{\gamma}$) as a adipocyte differentiation marker, and adiponectin was examined using western blot in differentiated OP9 cells. Effects of related genes were confirmed by luciferase assay using reporter assay. Results : AP and AT was not toxic on OP9 and MG63 cells, but AT was a little cytotoxic to osteoclast at the dose of $100{\mu}g/m{\ell}$. They could inhibit differentiation of OP9 cells and osteoclast with results of oil red O staining and TRAP staining. By western blot, AP and AT decreased the expression of $PPAR{\gamma}$ and $C/EBP{\alpha}$ which is the key transcription factor in adipogenesis and adiponectin secretion. AT also inhibited the BMP-4 activity in luciferase assay. AP also inhibited BMP-4 and Wnt3a activity, stimulated ER-${\beta}$ activity but inhibited androgen receptor activity. Conclusions : These results show AP and AT can be useful in osteoporosis and obesity via inhibition of osteoclast and adipocyte differentiation.

• The Korean Journal of Physiology and Pharmacology
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• v.13 no.6
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• pp.417-424
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• 2009

Osteoclasts, derived from multipotent myeloid progenitor cells, play homeostatic roles in skeletal modeling and remodeling, but may also destroy bone in pathological conditions such as osteoporosis and rheumatoid arthritis. Osteoclast development depends critically on a differentiation factor, the receptor activator of NF-${\kappa}B$ ligand (RANKL). In this study, we found that the hexane soluble fraction of the common fig Ficus carica (HF6-FC) is a potent inhibitor of osteoclastogenesis in RANKL-stimulated RAW264.7 cells and in bone marrow-derived macrophages (BMMs). HF6-FC exerts its inhibitory effects by suppression of p38 and NF-${\kappa}B$ but activation of ERK. In addition, HF6-FC significantly decreased the expression of NFATc1 and c-Fos, the master regulator of osteoclast differentiation. The data indicate that components of HF6-FC may have therapeutic effects on bone-destructive processes such as osteoporosis, rheumatoid arthritis, and periodontal bone resorption.

• The korean journal of orthodontics
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• v.37 no.5
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• pp.351-363
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• 2007

The aim of this study was to evaluate pulp and periodontal changes following rapid tooth retraction by periodontal distraction after bone undermining surgery in young adult dogs. Methods: Alter extraction of second premolars, the interseptal bone mesial to the upper 3rd premolar was undermined. After activating the distraction appliance at 0.5 mm/day for six days, the dogs were sacrificed at 0, 1, 3, 5, 7, and 9 weeks during the consolidation period. Tissue changes of periodontium and pulp were evaluated radiologically, histologically, and immunohistochemically. Results: Digital subtraction radiography showed active bone formation in the stretched periodontal ligament from 0 - 4 weeks. Resorption of the alveolar bone, appearance of osteoclasts, and infiltration of inflammatory cells were observed just after the activation period at the pressure side, and distinctive bone formation was seen in the tension side of the periodontal ligament from 1 week. New bone formation was active at 1 - 3 weeks. The expression of calcitonin gene-related peptide in the experimental group was increased at the alveolar bone and pulp, and periodontal ligament at the pressure side from 0 - 1 week, and it decreased after 5 weeks to become similar to that of the control group. Conclusions: The results showed that rapid tooth movement using periodontal distraction can be new form of orthodontic tooth movement for accelerating normal bone formation.