• Journal of the Korean Society of Food Science and Nutrition
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• v.37 no.1
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• pp.16-19
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• 2008

Bone mass in adults decreases with age because of the imbalance between the rate of bone formation and resorption. We performed this study to investigate whether Asparagus cochinchinensis (Lour.) Merr. (ACAE) plays a role in osteoblasts differentiation and osteoclasts formation. Ethanol extract of ACAE showed increase in the differentiation and alkaline phosphatase activity of osteoblasts. Also, it decreased the number of tartrate-resistant acid phosphatase (TRAP)-positive multinucleated cells (OCLs) and TRAP activity. Therefore, ACAE has the potential to prevent bone-related diseases such as osteoporosis by increasing the differentiation of osteoblasts and reducing both the number and activity of osteoclasts.

• International Journal of Oral Biology
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• v.31 no.4
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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.

• Molecules and Cells
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• v.38 no.10
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• pp.904-910
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• 2015

Negative regulator of reactive oxygen species (NRROS) is known to repress ROS generation in phagocytes. In this study, we examined the roles of NRROS in both osteoclasts and osteoblasts. Our results demonstrate that NRROS negatively regulates the differentiation of osteoclasts, but not osteoblasts. Further, overexpression of NRROS in osteoclast precursor cells attenuates RANKL-induced osteoclast differentiation. Conversely, osteoclast differentiation is enhanced upon siRNA-mediated knock-down of NRROS. Additionally, NRROS attenuates RANKL-induced $NF-{\kappa}B$ activation, as well as degradation of the NOX1 and NOX2 proteins, which are required for ROS generation. Based on our observations, we present NRROS as a novel negative regulator of RANKL-induced osteoclastogenesis.

• The Journal of Korean Obstetrics and Gynecology
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• v.30 no.4
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• pp.1-17
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• 2017

Objectives: This study was conducted to evaluate the effects of Hyeolbuchugeo-tang (HBC) on Osteoporosis. Methods: We induced RAW 264.7 cells to differentiate to Osteoclasts by RANKL and treated RANKL-induced RAW 264.7 cells with HBC (0, 150, 350, $700{\mu}g/ml$). To measure osteoclast differentiation and activation, we counted TRAP (+) MNCs and measured mRNA expressions of its related genes (TRAP, MMP-9, cathepsin K, NFATc1, c-Fos, MITF, iNOS, COX-2, TNF-${\alpha}$) by RT-PCR. To assess bone resorption, the Bone pit formation were examined under a microscope. Results: HBC decreased TRAP (+) MNCs and inhibited mRNA expressions of TRAP, MMP-9, cathepsin K, NFATc1, c-Fos, MITF in osteoclast. And HBC inhibited Bone pit formation. Conclusions: HBC inhibited osteoclast differentiation and activation and bone resorption. Taken together, these results indicate that HBC might have potentials for prevention and treatment of Osteoporosis.

• Proceedings of the Korean Society of Applied Pharmacology
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• 2001.04a
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• pp.103-112
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• 2001

Bone homeostasis is maintained by a balance between activities of osteoblasts(bone forming cells) and osteoclasts (bone resorbing cells). The activities of these cells are closely regulated by multiple factors including hormones and cytokines. The cessation of estrogen at menopause disrupts the balanced regulation and is the main cause of osteoporosis in postmenopausal women. Recent molecular biological studies led to a discovery of tumor necrosis factor(TNF) and TNF receptor families genes that play critical roles in the regulation of osteoclast formation and function. RANKL (receptor activator of nuclear factor kappa B ligand; also called ODF, TRANCE, and OPGL) expressed on cells supporting osteoclast is essential for osteoclast differentiation, activation, and survival. RANK, the counter-receptor for RANKL, is expressed on progenitor and mature osteoclasts. The interaction between RANKL and RANK is requlated by a soluble decoy receptor OPG (osteoprotegerin). Gene knock out studies of these molecules showed profound effects on bone. These results prompted development of new strategies for treatment of bone diseases. Inhibition of osteoclast activity by blocking the RANKL-RANK interaction using OPG is being attempted. Research on the signaling pathways of RANK is also actively carried out. Screening natural products that inhibit the RANKL-RANK interaction or the activity of obteoclasts would be another effective means to a new drug target for bone resorbing diseases.

• Journal of Marine Bioscience and Biotechnology
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• v.5 no.4
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• pp.1-7
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• 2011

Bone health is maintained by balance between bone resorption and bone formation, and bone homeostasis requires balanced interactions between osteoblasts and osteoclasts. Most of drugs and functional foods for bone health have been developed as bone resorption inhibitors, which maintain bone mass by inhibiting the function of osteoclasts. The recent studies have shown beneficial effects of marine natural products on bone health. Therefore, this review is aimed to study effects of marine-derived natural substances on osteoarthritis inhibition via attenuation of MMPs and osteoblastic differentiation via activation of alkaline phosphatase (ALP), osteoclacin (OC), bone morphogenic protein-2 (BMP-2) as an important factor for bone formation, and mineralization. The present review can provide new insights in the osteoblastic differentiation of marine natural products and possibility for their application in bone health supplement.

• YAKHAK HOEJI
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• v.56 no.6
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• pp.347-351
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• 2012

5-Lipoxygenase (5-LO) catalyzes the formation of two major groups of leukotrienes, LTB4 and cysteinyl leukotrienes (CysLT), and it has been implicated as a promising drug target to treat various inflammatory diseases. Since its role in mature osteoclasts (mOCs) had not been reported, we investigated the effect of 5-LO inhibitors on mOCs. We showed that 5-LO inhibitors dose-dependently decreases the number of mOCs. The effects of 5-LO inhibitors were reversible, suggesting that they did not cause any cellular damages in mOCs. We further demonstrated that the suppression of mOCs by 5-LO inhibitors was caused mainly by disruption of the actin ring formation. Similar effects were shown with CysLT receptor (CysLTR)1 antagonist in mOCs. The mRNA expression of CysLTR1 and the production of CysLT were increased in mOCs. These results indicate that CysLTR1 mediates the suppression of mOCs by 5-LO inhibitors. Taken together, this study demonstrated that 5-LO plays important role in mOCs and possibly a novel therapeutic target for bone resorption diseases.

• The Journal of Internal Korean Medicine
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• v.40 no.1
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• pp.58-69
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• 2019

Objective: This study investigated the effects of Hansu-Daebowon (HDW) on bone resorption in vitro and bone loss in vivo. Methods: Osteoclast differentiation was measured by counting TRAP (+) MNC formed from RAW 264.7 in the presence of RANKL. Bone pit formation was determined in an artificial bone slice loaded with RANKL-stimulated osteoclasts. To elucidate the mechanisms of the inhibitory effects of HDW on bone resorption and osteoclast differentiation, osteoclastogenic genes (i.e. TRAP, MMP-9, NFATc1, c-Fos, and Cathepsin K) were measured using real time PCR. Furthermore, bone loss was observed using micro-CT in an LPS-treated mammal model. Results: HDW inhibited the bone pit formation in vitro and inhibited bone loss in vivo. Moreover, HDW decreased the number of TRAP (+) MNCs in the presence of RANKL, and HDW inhibited the expressions of cathepsin K, MMP-9, TRAP, NFATc1, and c-Fos in the osteoclasts. Conclusion: HDW exerts inhibitory effects on bone loss and bone resorption resulting from the inhibitions of osteoclast differentiation and osteoclastogenic gene expression.

• BMB Reports
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• v.53 no.12
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• pp.646-651
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• 2020

Bone resorption is linked to bone formation via temporal and spatial coupling within the remodeling cycle. Several lines of evidence point to the critical role of coupling factors derived from pre-osteoclasts (POCs) during the regulation of bone marrow-derived mesenchymal stem cells (BMMSCs). However, the role of glial cell-derived neurotrophic factor (GDNF) in BMMSCs is not completely understood. Herein, we demonstrate the role of POC-derived GDNF in regulating the migration and osteogenic differentiation of BMMSCs. RNA sequencing revealed GDNF upregulation in POCs compared with monocytes/macrophages. Specifically, BMMSC migration was inhibited by a neutralizing antibody against GDNF in pre-osteoclast-conditioned medium (POC-CM), whereas treatment with a recombinant GDNF enhanced migration and osteogenic differentiation. In addition, POC-CM derived from GDNF knock-downed bone marrow macrophages suppressed BMMSC migration and osteogenic differentiation. SPP86, a small molecule inhibitor, inhibits BMMSC migration and osteogenic differentiation by targeting the receptor tyrosine kinase RET, which is recruited by GDNF into the GFRα1 complex. Overall, this study highlights the role of POC-derived GDNF in BMMSC migration and osteogenic differentiation, suggesting that GDNF regulates bone metabolism.

• IMMUNE NETWORK
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• v.22 no.5
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• pp.43.1-43.12
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• 2022

Osteoclasts (OCs) are clinically important cells that resorb bone matrix. Accelerated bone destruction by OCs is closely linked to the development of metabolic bone diseases. In this study, we screened novel chemical inhibitors targeting OC differentiation to identify drug candidates for metabolic bone diseases. We identified that 1,3-dibenzyl-5-fluorouracil, also named OCI-101, is a novel inhibitor of osteoclastogenesis. The formation of multinucleated OCs is reduced by treatment with OCI-101 in a dose-dependent manner. OCI-101 inhibited the expression of OC markers via downregulation of receptor activator of NF-κB ligand and M-CSF signaling pathways. Finally, we showed that OCI-101 prevents ovariectomy-induced bone loss by suppressing OC differentiation in mice. Hence, these results demonstrated that OCI-101 is a good drug candidate for treating metabolic bone diseases.