• Nutrition Research and Practice
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• v.18 no.1
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• pp.19-32
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• 2024

BACKGROUND/OBJECTIVES: Atherosclerosis is associated with increased inflammation in the visceral adipose tissue (VAT). Vitamin D has been reported to modulate the inflammatory responses of stromal vascular cells (SVCs) and adipocytes in adipose tissue, but the role of vitamin D in atherosclerosis biology is unclear. This study examined the effects of in vitro 1,25-dihydroxyvitamin D₃ (1,25[OH]₂D₃) treatment on the inflammatory responses of SVCs and adipocytes from atherosclerotic mice. MATERIALS/METHODS: C57BL/6J (B6) mice were divided randomly into 2 groups and fed a 10% kcal fat control diet (control group, CON) or 41% kcal fat, 0.21% cholesterol (high fat + cholesterol, HFC) diet (obese group, OB), and B6.129S7-Ldlr^tm1Her/J (Ldlr^-/-) mice were fed a HFC diet (obese with atherosclerosis group, OBA) for 16 weeks. SVCs and adipocytes isolated from VAT were pre-incubated with 1,25(OH)₂D₃ for 24 h and stimulated with lipopolysaccarides for the next 24 h. Proinflammatory cytokine production by adipocytes and SVCs, the immune cell population in SVCs, and the expression of the genes involved in the inflammatory signaling pathway in SVCs were determined. RESULTS: The numbers of total macrophages and SVCs per mouse were higher in OB and OBA groups than the CON group. The in vitro 1,25(OH)₂D₃ treatment significantly reduced macrophages/SVCs (%) in the OBA group. Consistent with this change, the production of interleukin-6 and monocyte chemoattractant protein 1 (MCP-1) by SVCs from the OBA group was decreased by 1,25(OH)₂D₃ treatment. The 1,25(OH)₂D₃ treatment significantly reduced the toll-like receptor 4 and dual-specificity protein phosphatase 1 (also known as mitogen-activated protein kinase phosphatase 1) mRNA levels in SVCs and MCP-1 production by adipocytes from all 3 groups. CONCLUSIONS: These findings suggest that vitamin D can attribute to the inhibition of the inflammatory response in VAT from atherosclerotic mice by reducing proinflammatory cytokine production.

• Journal of Ginseng Research
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• v.39 no.1
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• pp.46-53
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• 2015

Background: Glucocorticoids (GCs) are commonly used in many chemotherapeutic protocols and play an important role in the normal regulation of bone remodeling. However, the prolonged use of GCs results in osteoporosis, which is partially due to apoptosis of osteoblasts and osteocytes. In this study, effects of Korean Red Ginseng (KRG) on GC-treated murine osteoblastic MC3T3-E1 cells and a GC-induced osteoporosis mouse model were investigated. Methods: MC3T3-E1 cells were exposed to dexamethasone (Dex) with or without KRG and cell viability was measured by the 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay. Realtime polymerase chain reaction was performed to evaluate the apoptotic gene expression; osteogenic gene expression and alkaline phosphatase (ALP) activity were also measured. Western blotting was performed to evaluate the mitogen-activated protein kinase (MAPK) proteins. A GC-induced osteoporosis animal model was used for in vivo study. Results and conclusion: The MTT assay revealed that Korean Red Ginseng (KRG) prevents loss of cell viability caused by Dex-induced apoptosis in MC3T3E1 cells. Real-time polymerase chain reaction data showed that groups treated with both Dex and KRG exhibited lower mRNA levels of caspase-3 and -9, whereas the mRNA levels of Bcl2, IAPs, and XIAP increased. Moreover, groups treated with both Dex and KRG demonstrated increased mRNA levels of ALP, RUNX2, and bone morphogenic proteins as well as increased ALP activity in MC3T3-E1 cells, compared to cells treated with Dex only. In addition, KRG increased protein kinase B (AKT) phosphorylation and decreased c-Jun N-terminal kinase (JNK) phosphorylation. Moreover, microcomputed tomography analysis of the femurs showed that GC implantation caused trabecular bone loss. However, a significant reduction of bone loss was observed in the KRG-treated group. These results suggest that the molecular mechanism of KRG in the GC-induced apoptosis may lead to the development of therapeutic strategies to prevent and/or delay osteoporosis.

• Korean Journal of Medicinal Crop Science
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• v.19 no.6
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• pp.491-500
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• 2011

Ursolic acid, triterpenoid compound has been shown to stimulate osteoblast differentiation and enhance bone formation. In the present study, we examined the effects of similar triterpenoid compounds, oleanolic acid (OA) and its derivatives, such as oleanolic acid acetate (OAA) and oleanolic acetate methyl ester (OAM) on the bone formation in MC3T3-E1 osteoblast cells. We determined cellular proliferation, alkaline phosphatase (ALP) activity, mineralization, and expression of osteoblast specific genes and mitogen activated protein kinase phosphorylation. Treatment of $0.1-10{\mu}m$ OA, OAA, and OAM increased cellular proliferation, but not significantly increased as compared with dimethyl sulfoxide (DMSO). OA, OAA, and OAM at 5uM concentration enhanced ALP expression, mineralization, and osteocalcin (OCN) mRNA level. In conclusion, OA and its derivatives stimulated the osteoblast differentiation by increasing ALP, mineralization, and OCN mRNA expression. However, there were no significantly difference on osteoblast differentiation among treatment of OA, OAA, and OAM.

• 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.

• Journal of Life Science
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• v.30 no.11
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• pp.983-989
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• 2020

The balance between bone-resorbing osteoclasts and bone-forming osteoblasts is key to bone health. An imbalance between osteoclasts and osteoblasts leads to various bone-related disorders, such as osteoporosis, osteomalacia, and osteopetrosis. However, the bone-resorption inhibitor drugs that are currently used may cause side effects. Natural substances have recently received much attention as therapeutic drugs for the treatment of bone health. This study was designed to determine the effect of Tenebrio molitor larvae ethanol extract (TME) on receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclast differentiation. To measure the effect of TME on osteoclast differentiation, RAW264.7 cells were treated with RANKL with or without TME for 5 days. The tartrate-resistant acid phosphatase (TRAP) activity was significantly inhibited by treatment of TME without cytotoxicity up to 2 mg/ml. In addition, TME effectively suppressed expression of osteoclast differentiation-related marker genes and proteins such as TRAP, NFATc1, and c-Src. TME also significantly inhibited the p38 mitogen-activated protein kinase (MAPK) signaling pathway without affecting ERK and JNK signaling in RANKL-induced RAW264.7 cells. Consequently, we conclude that TME suppresses osteoclast differentiation by inhibiting RANKL-induced osteoclastogenic genes expression through the p38 MAPK signaling pathways. These results suggest that TME and its bioactive components are potential therapeutics for bone-related diseases such as osteoporosis.