• 대한의용생체공학회:의공학회지
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• 제30권1호
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• pp.89-93
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• 2009

Bone remodeling is a continuous process of skeletal renewal during which bone formation is tightly coupled to bone resorption. Mechanical loading is an important regulator of bone formation and resorption. In recent studies, neurotransmitters such as vasoactive intestinal peptide (VIP) were found to be present inside bone tissue and have been suggested to potentially regulate bone remodeling. In this study, our objective was to use a pre-established in vitro oscillatory fluid flow-induced shear stress mechanical loading system to quantify the effect of VIP on bone resorptive activity and investigate its combined effect with mechanical loading. VIP decreased osteoclastogenesis significantly decreased RANKL/OPG mRNA ration by approximately 90%. Combined VIP and mechanical loading further decreased RANKL/OPG ratio to approximately 95%. These results suggest that VIP present in bone tissue may synergistically act with mechanical loading to regulate bone remodeling via suppression of bone resorptive activities.

• 한국식품영양과학회지
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• 제39권3호
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• pp.363-368
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• 2010

본 연구에서는 마우스 골수유래 파골세포와 난소절제 동물모델을 이용하여 애엽 추출물이 골대사에 미치는 영향을 살펴보았다. 애엽 추출물이 파골세포의 분화 및 활성에 미치는 영향을 알아보기 위하여 마우스 골수유래 전구세포에 M-CSF와 RANKL을 처리하여 파골세포로의 분화를 유도한 후, TRAP 염색법을 실시하고 TRAP 활성도를 측정하였다. 그 결과 애엽 추출물은 TRAP 양성 다핵세포의 형성과 TRAP 활성을 농도 의존적으로 감소시켰으며, 파골세포의 골흡수 또한 애엽 추출물의 최고농도($30\;{\mu}g/mL$) 처리 시약 90%까지 억제되는 것을 확인하였다. 난소절제 동물모델을 이용한 실험에서도 애엽 추출물이 난소절제에 따른 급격한 골밀도 감소를 막아준다는 사실을 확인할 수 있었다. 이상의 결과로 미루어 볼 때, 애엽 추출물이 에스트로겐 분비 감소로 인하여 급격한 골 손실이 나타나는 폐경기 여성의 골다공증 예방에 효과가 있을 것으로 사료된다.

• International Journal of Oral Biology
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• 제31권4호
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• pp.119-125
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• 2006

The importance of phytoestrogens to human health is currently being actively investigated. Hesperidin, abundantly found in citrus fruits, is known to possess antioxidant, anticancer, and anti-inflammatory effects. Recently, it has been reported that hesperidin inhibits bone loss and decreases serum and hepatic lipids in ovariectomized mice. In our study, to determine the possible role of hesperidin in the regulation of bone metabolism, we observed the effects of hesperidin on the proliferation and activity of osteoblasts, as well as the effects of hesperidin on osteoclast generation and activity. We observed that, when treated with hesperidin, the number and viability of osteoblastic cells increased, alkaline phosphatase (ALP) activity of osteoblastic cells increased, and osteoprotegerin (OPG) secretion from MG63 cells decreased. Hesperidin treatment had no effect on the osteoclast generation and activity in the bone marrow cell culture, but decreased the number and resorptive activity of osteoclasts generated from RAW/264.7 cells. Taken together, these results indicate that hesperidin increases the proliferation and activity of osteoblasts, while inhibiting generation and activity of osteoclasts. Although the precise role of hesperidin remains to be elucidated, our study suggests that it is one of the important modulators of bone metabolism.

• BMB Reports
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• 제43권8호
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• pp.524-529
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• 2010

Glucocorticoids (GCs) are useful drugs for the treatment of various diseases, but their use for prolonged periods can cause severe side effects such as osteoporosis. GCs have a direct effect on bone cells, where they can arrest bone formation, in part through the inhibition of osteoblast. On the other hand, GCs potently suppress osteoclast resorptive activity by disrupting its cytoskeleton based on the inhibition of RhoA, Rac and Vav3 in response to macrophage colony-stimulating factor. GCs also interfere with microtubule distribution and stability, which are critical for cytoskeletal organization in osteoclasts. Thus, GCs inhibit microtubule-dependent cytoskeletal organization in osteoclasts, which, in the context of bone remodeling, further dampens bone formation.

• Restorative Dentistry and Endodontics
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• 제25권1호
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• pp.63-70
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• 2000

The properties of ideal retrograde filling materials include the ability to seal the root canal system in three dimensions and well tolerated by periradicular tissues. Biocompatibility testing has been done mainly with cytotoxicity tests using cell culture. Little attention has been paid to the potential adverse influence on the inflammatory and immune reaction in the periapical tissue. The purpose of this study was to investigate the effects of retrograde filling materials on human mononuclear cells in vitro. Freshly mixed and set specimens from six materials (Z100, Tetric Ceram, Fuji II, Fuji II LC, F2000, Compoglass Flow, and ZOE) were eluated with cell culture medium for 24 hours. Cytotoxic effects of these extracts were evaluated by determining cell viability and enzyme activity using MTT and lactate dehydrogenase (LD). The production of inflammatoy bone resorptive cytokine, TNF-${\alpha}$ was measured from human peripheral blood mononuclear cells (PBMC) exposed to the extracts by means of Endogen Human TNF-${\alpha}$ ELISA kit (Wobrun, MA, U.S.A.). Eluates and diluted (1 : 10) eluates with cell culture medium from freshly mixed Fuji IT had cytotoxic effects on mononuclear cells using MTT and LD. However, eluates from set Fuji II were not cytotoxic. Eluates form set ZOE exhibited cytotoxicity with LD test. TNF-${\alpha}$ levels were high in eluates from freshly mixed Fuji II and Z100. Diluted eluates from freshly mixed Z100 and F2000 stimulated the production of TNF-${\alpha}$. However, there were no significant difference in TNF-${\alpha}$ levels compared to controls. These results indicate that some materials could possibly stimulate bone resorption in the periapical tissue by means of the production of bone resorptive cytokine.

• 동의생리병리학회지
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• 제23권6호
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• pp.1299-1304
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• 2009

We have previously shown that water extract of deer antler (WEDA) inhibited RANKL-mediated osteoclast differentiation from bone marrow macrophages by suppressing c-Fos and NFATc1 expression. Thus, we examined the effect of WEDA in inflammation-induced bone loss in vivo. Here we found that WEDA inhibited osteoblast-supported osteoclast differentiation induced by lipopolysaccharide (LPS). However, WEDA did not suppress the expression of receptor activator of NF-${\kappa}B$ ligand (RANKL) in response to LPS in osteoblasts. WEDA also inhibited the bone resorptive activity of mature osteoclasts. To examine the effect of WEDA on bone loss, when LPS injected subcutaneously in mice, bone loss was greatly increased, but WEDA treatment inhibited LPS-mediated bone loss. Taken together, we conclude that WEDA inhibited osteoclast differentiation and bone resorption in vitro and in vivo. Thus WEDA may be useful in the treatment of bone-related disorders.

• 한국한의학연구원논문집
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• 제13권2호통권20호
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• pp.157-164
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• 2007

An imbalance in bone remodeling that is caused by increased bone resorption over bone formation leads to most adult skeletal diseases including osteoporosis. Since the development of anti-resorptive agents from natural substances has recently gained more interest in the treatment of osteoporosis, we evaluated the effects of 222 natural compounds on receptor activator of $NF-{\kappa}B$ ligand (RANKL)-induced of tartrate-resistance acid phosphatase (TRAP) activity in RAW264.7 murine macrophage cell, and found that berberine chloride is one of compounds inhibiting RANKL-induced TRAP activity. Berberine chloride significantly inhibited the RANKL-induced TRAP activity and the formation of multinucleated osteoclasts in a dose-dependent manner. In addition, berberine chloride prevented the RANKL-induced mRNA expression of TRAP, matrix metalloproteinase 9 and c-Src, which have been known to be highly expressed in the process of osteoclastogenesis. Interestingly, berberine chloride prevented the RANKL-induced activation of extracellular signal-regulated kinase (ERK) which is one of mitogen-activated protein (MAP) kinases. In conclusion, berberine chloride could inhibit the osteoclastogenesis via preventing the activation of ERK/MAP kinase signaling pathway.

• Journal of Periodontal and Implant Science
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• 제25권2호
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• pp.386-396
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• 1995

Interieukin 1${\beta}$ is a potent bone resorptive cytokine which mediates soft tissue destruction through the stimulatidn of prostaglandin production and the induction of collagenase. This constellation of activities suggests a role of IL-1${\beta}$ in the pathogenesis of periodontal disease. The purpose of this study was to evaluate the effects of herbal extracts on production and activity of IL-1${\beta}$. When LPS was added to cultured human blood monocytes, the effects of herbal extracts on the production of IL-1${\beta}$ was evaluate by thymocyte stimulation assay. When rHuIL-1${\beta}$ was added to cultured human gingival fibroblasts, the effects of herbal extracts on production of $PGE_2$ was evaluated by ELISA and when it was added to cultured mouse calvaria, the effects on bone resorption was estimated by .$^{45}Ca$-release bone resorption assay. The herbal extracts that had been used in this study were as follows; Asparagi Radix, Schzandrae Fractus, Zizyphi Fractus and Rhois Galla. The following results were obtained from this study. 1. All these extracts effectively inhibited the production of IL-1${\beta}$ on cultured human blood monocytes. 2. All these extracts effectively inibited the production of $PGE_2$ on cultured human gingival fibroblasts. 3. All these extracts did not effectively inhibit the bone resorption induced by rHulL-1${\beta}$ on cultured mouse calvaria.

• Journal of Korean Neurosurgical Society
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• 제46권1호
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• pp.45-51
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• 2009

Objective : To evaluate the potential effects of risedronate (RIS) which shows a higher anti-resorptive effect among bisphosphonates, after a posterolateral lumbar intertransverse process spinal fusion using both autograft and allograft in a rat model. Methods : A totoal of 28 Sprague-Dawley rats were randomized into 2 study groups. A posterolateral lumbar intertransverse process spinal fusion was peformed using both autograft and allograft in a rat model. Group I (control) received 0.1 mL of steril saline (placebo) and Group II (treatment) received risedronate, equivalent to human dose (10 ${\mu}g$/kg/week) for 10-weeks period. Results : The fusion rates as determined by manual palpation were 69% in the group I and 46% in the group II (p = 0.251). According to radiographic score, the spinal segment was considered to be fused radiographically in 7 (53%) of the 13 controls and 9 (69%) of the 13 rats treated with RIS (p = 0.851). The mean histological scores were 5.69 ${\pm}$ 0.13 and 3.84 ${\pm}$ 0.43 for the control and treatment groups, respectively. There was a significant difference between the both groups (p = 0.001). The mean bone density of the fusion masses was 86.9 ${\pm}$ 2.34 in the control group and 106.0 ${\pm}$ 3.54 in the RIS treatment group. There was a statistical difference in mean bone densities of the fusion masses comparing the two groups (p=0.001). Conclusion : In this study, risedronate appears to delay bone fusion in a rat model. This occurs as a result of uncoupling the balanced osteoclastic and osteoblastic activity inherent to bone healing. These findings suggest that a discontinuation of risedronate postoperatively during acute fusion period may be warranted.

• Molecules and Cells
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• 제37권8호
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• pp.628-635
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• 2014

2-(Trimethylammonium) ethyl (R)-3-methoxy-3-oxo-2-stearamidopropyl phosphate [(R)-TEMOSPho], a derivative of an organic chemical identified from a natural product library, promotes highly efficient megakaryopoiesis. Here, we show that (R)-TEMOSPho blocks osteoclast maturation from progenitor cells of hematopoietic origin, as well as blocking the resorptive function of mature osteoclasts. The inhibitory effect of (R)-TEMOSPho on osteoclasts was due to a disruption of the actin cytoskeleton, resulting from impaired downstream signaling of c-Fms, a receptor for macrophage-colony stimulating factor linked to c-Cbl, phosphoinositol-3-kinase (PI3K), Vav3, and Rac1. In addition, (R)-TEMOSPho blocked inflammation-induced bone destruction by reducing the numbers of osteoclasts produced in mice. Thus, (R)-TEMOSPho may represent a promising new class of antiresorptive drugs for the treatment of bone loss associated with increased osteoclast maturation and activity.