• Biomolecules & Therapeutics
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• v.32 no.2
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• pp.205-213
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• 2024

Hydroxychavicol, a primary active phenolic compound of betel leaves, previously inhibited bone loss in vivo by stimulating osteogenesis. However, the effect of hydroxychavicol on bone remodeling induced by osteoclasts is unknown. In this study, the anti-osteoclastogenic effects of hydroxychavicol and its mechanism were investigated in receptor activator of nuclear factor kappa-B ligand (RANKL)-induced osteoclasts. Hydroxychavicol reduced the number of tartrate resistance acid phosphatase (TRAP)-positive multinucleated, F-actin ring formation and bone-resorbing activity of osteoclasts differentiated from RAW264.7 cells in a concentration-dependent manner. Furthermore, hydroxychavicol decreased the expression of osteoclast-specific genes, including cathepsin K, MMP-9, and dendritic cell-specific transmembrane protein (DC-STAMP). For mechanistic studies, hydroxychavicol suppressed RANKL-induced expression of major transcription factors, including the nuclear factor of activated T-cells 1 (NFATc1), c-Fos, and c-Jun. At the early stage of osteoclast differentiation, hydroxychavicol blocked the phosphorylation of NF-κB subunits (p65 and Iκβα). This blockade led to the decrease of nuclear translocation of p65 induced by RANKL. In addition, the anti-osteoclastogenic effect of hydroxychavicol was confirmed by the inhibition of TRAP-positive multinucleated differentiation from human peripheral mononuclear cells (PBMCs). In conclusion, hydroxychavicol inhibits osteoclastogenesis by abrogating RANKL-induced NFATc1 expression by suppressing the NF-κB signaling pathway in vitro.

• Journal of Periodontal and Implant Science
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• v.33 no.4
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• pp.573-584
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• 2003

Bone remodeling results from the combined process of bone resorption and new bone formation which is regulated in part by some of Dexamethasone related proliferation & mineralization of cultured bone cell and polypeptide growth factors such as platelet derived growth factor(PDGF), which has been known to be an important local regulator of bone cell activity and participate in normal bone remodeling. To evaluate the effects of Dex and PDGF on bony healing of calvarial defect in rats, 10 ng/ml PDGF were applied on P group and 10 ng/ml PDGF and $10^7$ M Dex were applied PD group. 4 rats in each group were sacrificed at 7, 14. 21 days after operation respectively, and the tissue blocks were prepared for light microscope with H-E for evaluation of overall healing, with TRAP(tartrate resistant acid phosphatase) for evaluation of osteoclastic activity and with immunohistochemical staining for macrophages. The results were as follows : 1. In all group, healing aspects were progressed from 7 days to 21 days in soft and bony tissue, but complete repair were not observed in bony defect 2. PDGF and control group were showed similar bony healing aspect , but bony healing in combination of PDGF-BB and Dex were observed slower aspect compared to PDGF and control group from early healing times. 3. There were no significant difference on activities of osteoclast and macrophages in bony healing between control and experimental group In conclusion, PDGF were not influenced on bony healing of defect and combination of PDGF-BB and Dex were showed slower healing through early healing times. it was considered that Dex compared to PDGF did influenced on early hone formation factors in healing period

• Maxillofacial Plastic and Reconstructive Surgery
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• v.29 no.4
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• pp.333-339
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• 2007

Adequate bone quantity is one of the important factor to obtain osseointegration after implantation. Guided bone regeneration (GBR) has widely used in implantation for reconstruction of bony defects. Since introducing this procedure, there are many studies about survival rate of implants, changing in surrounding bone volume after function. The purpose of this study was to evaluate the amount of resorption according to placement timing and survival rate after function. The subjects were patients who had been operated with GBR from Jun 2003 to Jun 2004 in Seoul National University Bundang Hospital. They were divided into simultaneous and delayed placement group. The follow up had been performed at the time of just after GBR, 1, 3, 6, 12, 24-month later and standard periapical radiographs were taken to estimate the bone level at the time. The total average of bone level change in radiographs was 1.94mm(${\pm}0.25$), and 1.92mm(${\pm}0.72$) in simultaneous installation, 2.03mm(${\pm}0.25$) in delayed installation. In this report, the survival rates were 92.2% in simulataneous group and 92.3% in delayed group. Insufficient primary stability, early contamination of wound, overloading, poor oral hygiene, and infection were thought to be associated factors in the failed cases.

• The Journal of the Korean dental association
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• v.52 no.4
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• pp.218-233
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• 2014

Bispbosphonates are a class of pharmaceutic agents, which induce apoptosis of osteoclast as well as impair osteoclastic activity to suppress bone resorption. Thus, bisphophonates are effectively used to treat osteoporosis, multiple myeloma and to prevent bone metastases of malignant cancer. However, recently dental disease have been reported associated with Bisphosphonates. Thus, there are a number of discussions about proper prevention and treatment of bisphosphonate-related osteonecrosis of jaw(BRONJ). Marshall R. Urist in 1965 made the seminal discovery that a specific protein, BMP(bone morphogenetic protein), found in the extracellular matrix of demineralized bone could induce bone formation newly when implanted in extraosseous tissues in a host. BMPs are multi-functional growth factors which are members of the transforming growth factor-beta super family and their ability is that plays a pivotal roll in inducing bone. About 18 BMP family members have been identified and characterized. Among of them, BMP-2 and BMP-7 have significant importance in bone development. In this study, patients of BRONJ were recieved who visited Department of oral and maxillofacial surgery, school of dentistry, Wonkwang university for past 3 years from 2011 to 2013. We focused on the results of the surgical intervention. We suggest that new strategy of treatment used to rhBMP-2 and LFA(Lidocaine-Fibrinogen-Aprotinin)-collagen scaffold for patients of BRONJ. The purpose of this paper is to give a brief overview of BMPs and to critically review the clinical data currently available on rhBMP-2 and LFA collage scaffold.

• Journal of Periodontal and Implant Science
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• v.38 no.sup2
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• pp.395-404
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• 2008

Purpose: Osteoprotegerin (OPG) is a secreted glycoprotein and a member of the tumor necrosis factor (TNF) receptor family that inhibits bone resorption by suppressing osteoclastogenesis. Gingival fibroblasts (GF) play a role in periodontal disease progression, and the purpose of this experiment was to evaluate influence of osteotropic factors on the expression of osteoprotegerin mRNA in these cells. Materials and Methods: In this experiment, the influence of osteoclastogenic factors, interleukin-1 beta (IL-$1{\beta}$), TNF-$\alpha$, prostanglandin E2 ($PEG_2$). parathyroid hormone (PTH) and 1$\alpha$, 25-dihydroxyvitamin $D_3$ on the expression of osteoprotegerin mRNA in GF was studied by Northern blot hybridization. Results: As expected, $PEG_2$ tended to inhibit OPG levels and this was most prominent at 24 hours of culture with $10^{-7}M$ of $PEG_2$. TNF-$\alpha$ at 10ng/ml and also at 25ng/ml decreased OPG levels to almost 30% of the control at 24 hours. This contrasts with reports of increased OPG levels from osteoblast/stromal cells and gingival fibroblasts stimulated by TNF-$\alpha$. Decrease of OPG levels with $PEG_2$ and TNF-$\alpha$ suggests a pathway whereby these mediators exert their resorptive effects. However, OPG levels were increased almost 3-fold at 24 hours with IL-1$\beta$(1 to 15ng/ml) and increased 1.4 fold with 24-hour treatment of $10^{-7}M$ PTH. Conclusion: Increase of OPG levels suggests that these 'osteoclastogenic' factors act in more complex ways and may act to inhibit bone resorption in inflammatory periodontitis. This result supports the role of OPG as a negative feedback mechanism in osteoclastic activity.

• Natural Product Sciences
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• v.26 no.1
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• pp.83-89
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• 2020

Osteoporosis is a worldwide disease leading to significant economic and societal burdens globally. Osteoporosis is caused by unbalanced bone remodeling between the rate of osteoclast bone resorption and osteoblast bone formation. Acer tegmentosum Maxim (AT) is a traditional herbal medicine containing multiple biological activities such as anti-oxidant and anti-inflammatory purposes. However, its role in osteoporosis has not been fully studied. Therefore, we investigated whether AT has a potent inhibitory effect on osteoporosis and its mechanism through a systemic evaluation in ovariectomized (OVX) mice. OVX mice were orally administrated with the AT at doses of 50, 100, and 200 mg/kg for 10 weeks. Histological images and histomorphometry analyses were performed by H&E and Toluidine blue satin, and the expression levels of receptor activator for nuclear factor-kB ligand (RANKL), nuclear factor of activated T cells cytoplasm 1 (NFATc1), c-Fos, and matrix metalloproteinase 9 (MMP9) related to the osteoclast differentiation were investigated using immunohistochemical analysis. Administration of AT prevented bone loss and the alternations of osteoporotic bone parameters at the distinct regions of the distal femur and spongiosa region in OVX mice. Further, administration of AT increased periosteal bone formation in a dose-dependent manner. Meanwhile, AT inhibited not only the expression of NFATc1 and c-Fos, which are two major regulators of osteoclastogenesis but also reduced bone resorbed encoding expression of MMP9 and RANKL. Our results indicated that administration of AT prevented bone loss and the alternations of osteoporotic bone parameters at the distinct regions of the distal femur and spongiosa region in OVX mice. Also AT has the bone protective effect through the suppression of osteoclast and promotion of osteoblast, suggesting that it could be a preventive and therapeutic candidate for anti-osteoporosis.

• Journal of Nutrition and Health
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• v.41 no.3
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• pp.199-205
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• 2008

The overall purpose of this study was to investigate the effects of level of isoflavones supplementation on bone metabolism in growing female rats. Forty-five rats divided into three groups; Control, l/2IF, and lIF. Serum osteocalcin and alkaline phosphatase (ALP) activity, urinary deoxypyridinoline (DPD) crosslinks value were measured to monitor bone formation and resorption at the ninth week after feeding. Hormones related to bone metabolism were determined, included parathyroid hormone (PTH) , calcitonin, estradiol, growth hormone and insulin-like growth factor I (IGF-I). The results of this study were as follows: the isoflavones intake level did not affect weight gain, mean food intake and food efficiency ratio. The serum concentration of osteocalcin and the activity ofALP were not significantly different by different levels of isoflavones supplementation. The urinary DPD crosslinks value was not significantly different by different levels ofisoflavones supplementation. There were no significant differences in serum PTH, estradiol and IGFI among all groups. However, calcitonin was shown significantly higher in the groups of lIF and l/2IF than control group. And growth hormone was shown significantly higher in the groups of lIF than control group. (Korean J Nutr 2008; 41(3): 199~205)

• Korean Journal of Acupuncture
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• v.37 no.2
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• pp.63-75
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• 2020

Objectives : Osteoporosis is the most common bone disease and osteoporosis fracture is the leading cause of decreased life. Bisphosphonate and selective estrogen receptor modulators are the best choice of treatment for osteoporosis. However, when used for a long time, they increase the probability of side effect such as osteonecrosis of the jaw. Thus, it is crucial to develop alternative medicine to treat osteoporosis. Gentianae Macrophyllae Radix, a herbal medicine, is mainly to treat rheumatoid arthritis. However, the effect of the water extract of Gentianae Macrophyllae Radix (w-GM) on osteoporosis has not been investigated. Thus, we examine whether w-GM can inhibit osteoclast differentiation and bone resorption on receptor activator of nuclear factor kappa-B (NF-κB) ligand (RANKL)-treated RAW 264.7 cells. In this study, RAW 264.7 cells were used as an osteoclast differentiation model by treating them with RANKL. Methods : RAW 264.7 cells were used to determine the effect of w-GM on osteoclast differentiation and bone resorption. The number of tartrate-resistant acid phosphatase (TRAP)-positive cells, TRAP activity and pit formation assay were examined. In addition, protein expressions were measured by western blot and mRNA expressions were analyzed by reverse transcription polymerase chain reaction. Results : Treatment with w-GM inhibited the number of TRAP-positive cells, TRAP activity and pit area. In addition, w-GM decreased protein expression such as mitogen-activated protein kinase, NF-κB, c-Fos and nuclear factor of activated T-cells cytoplasmic 1 (NFATc1). It also inhibited the mRNA levels such as c-Fos, NFATc1, TRAP, NF-κB, calcitonin receptor and cathepsin K in RANKL-treated RAW 264.7 cells. Conclusions : These results suggest that w-GM has inhibitory effects via osteoclast differentiation, thus it could be a new medication for osteoporosis.

• Experimental and Molecular Medicine
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• v.50 no.12
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• pp.3.1-3.14
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• 2018

Type 1 diabetes mellitus (T1DM) is a pathological condition associated with osteopenia. $WNT/{\beta}$-catenin signaling is implicated in this process. Trabecular and cortical bone respond differently to $WNT/{\beta}$-catenin signaling in healthy mice. We investigated whether this signaling has different effects on trabecular and cortical bone in T1DM. We first established a streptozotocin-induced T1DM mouse model and then constitutively activated ${\beta}$-catenin in osteoblasts in the setting of T1DM (T1-CA). The extent of bone loss was greater in trabecular bone than that in cortical bone in T1DM mice, and this difference was consistent with the reduction in the expression of ${\beta}$-catenin signaling in the two bone compartments. Further experiments demonstrated that in T1DM mice, trabecular bone showed lower levels of insulin-like growth factor-1 receptor (IGF-1R) than the levels in cortical bone, leading to lower $WNT/{\beta}$-catenin signaling activity through the inhibition of the IGF-1R/Akt/glycogen synthase kinase $3{\beta}$ ($GSK3{\beta}$) pathway. After ${\beta}$-catenin was activated in T1-CA mice, the bone mass and bone strength increased to substantially greater extents in trabecular bone than those in cortical bone. In addition, the cortical bone of the T1-CA mice displayed an unexpected increase in bone porosity, with increased bone resorption. The downregulated expression of WNT16 might be responsible for these cortical bone changes. In conclusion, we found that although the activation of $WNT/{\beta}$-catenin signaling increased the trabecular bone mass and bone strength in T1DM mice, it also increased the cortical bone porosity, impairing the bone strength. These findings should be considered in the future treatment of T1DM-related osteopenia.

• Journal of Periodontal and Implant Science
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• v.30 no.2
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• pp.347-360
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• 2000

Bone remodeling results from the combined process of bone resorption and new bone formation which is regulated in part by some of the polypeptide growth factors such as platelet derived growth factor(PDGF), which has been known to be an important local regulator of bone cell activity and participate in normal bone remodeling. This process includes strictly regulated gene expression of several bone matrix proteins such as type I collagen and osteopontin, a 44 kDa phosphorylated glycoprotein, which has important roles in bone formation. The purpose of this study is to evaluate the effecs of PDGF-BB on the mRNA expression of bone matrix protein, type I collagen and osteopontin, in MC3T3- E1 cell culture. Cells were seeded at $5{\times}10^5$ cells in 10 ml of minimum essential medium alpha(${\alpha}-MEM$) containig 10% fetal bovine serum, 10 mM beta glycerophosphate. 0.1, 1, 10 ng/ml PDGF-BB were added to the cells for the day 3, 7, 14, 21, 28 and cultured for 24 hours. Type I collagen cDNA, Hf677, and osteopontin cDNA were used as probes for northern blot analysis. Total cellular RNA was purified at indicated day and northern blot analysis was performed. The results were as follows : Type I collagen mRNA expressions were higher at the day 3 and 7, and lower in the day 14, 21 in the control groups. In the experimental groups, mRNA expressions were increased when 0.1 ng/ml PDGF-BB were added on the day 3, 7, 21, and decreased in dose-dependent manner on the day 14, decreased at all added dose on the day 28. Osteopontin mRNA expressions were highest in the day 21 groups and lowest in the day 14 groups in the control groups. Interesting results were shown in the day 14 and 21 groups. We found that osteopontin mRNA level was increased in dose dependent manner in the day 14 groups, and decreased dose dependent manner in the day 21 groups. In conclusion, PDGF-BB may have various control effects on type I mRNA expression in the growth and differentiation process of MC3T3-E1 cells and may have contrary regulatory effects on osteopontin mRNA expression. For examples, when the baseline level of osteopontin mRNA was low, as in the day 14, PDGF-BB up-regulated osteopontin mRNA expression in dose dependent manner, and when the baseline level was high as in the day 21, PDGF-BB down-regulated dose dependent manner. Thus, it may be useful for clinical application in periodontal regeneration procedure if further study were performed.