• Nutrition Research and Practice
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• 제13권6호
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• pp.480-487
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• 2019

BACKGROUND/OBJECTIVES: Osteoarthritis (OA) is a major public health issue in Japan and other countries, and foods that prevent or treat OA are in strong demand. Proteins and peptides in chicken meat and bones are known for being rich in functional and nutritional ingredients for the improvement of osteoporosis. We speculated that chicken legs, a food consumed in many regions of the world, may also contain such ingredients. In this study, we aim to (i) evaluate the effect of chicken leg extract (CLE) on the promotion of cartilage matrix production and (ii) identify the active ingredient in CLE that contributes to this function. MATERIALS/METHODS: Artificial CLE digest was prepared, and the acid mucopolysaccharide production-promoting activity of the CLE digest was evaluated by alcian blue staining of ATDC5 cells. CLE was orally administered to rabbits with burr holes in the knee joint of the femur, and the degree of regeneration of cartilage matrix was evaluated. Furthermore, we investigated orally administered CLE-derived peptides in human plasma using LC-MS. From measuring the acid mucopolysaccharide production-promotion activity of these peptides, a molecule considered to be an active ingredient in the CLE digest was identified. RESULTS: CLE digest promoted acid mucopolysaccharide production and facilitated regeneration of cartilage matrix in in vitro and in vivo experiments. Four peptides including phenylalanyl-hydroxyproline (Phe-Hyp) were detected as CLE-derived peptides in human plasma. The effect of CLE was inferred to be due to Phe-Hyp, which was confirmed to be present in the CLE digest. CONCLUSIONS: It was shown that CLE stimulated the production of articular cartilage matrix both in vitro and in vivo, and that CLE could be an effective food for preventing or treating OA. Furthermore, only Phe-Hyp was confirmed as the active compound in the CLE digest, suggesting that the activity of CLE was due to Phe-Hyp.

• 약학회지
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• 제59권2호
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• pp.59-65
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• 2015

KR-67500, trans-4-(2-(4-methyl-1,1-dioxido-6-(2,4,6-trichlorophenyl)-1,2,6-thiadiazinan-2-yl)acetamido)adamantane-1-carboxamide, is a novel $11{\beta}$-HSD1 inhibitor with its therapeutic effects of its anti-diabetic, anti-adipogenic and anti-osteoporotic activity. This study was performed to evaluate in vitro and in vivo pharmacokinetic properties of KR-67500 as a new drug candidate. KR-67500 was stable and highly bound to proteins in rat plasma. The microsomal stabilities of KR-67500 in human and rat liver were high. The inhibitory effect of KR-67500 for five cytochrome P450 enzymes was low. Preclinical pharmacokinetic studies have been carried out with intravenous or oral administrations of KR-67500 (10 mg/kg) to male rats and monkey. KR-67500 showed low clearance (0.68 l/h/kg) and high oral bioavailability (102%) in male rats. These results suggest that KR-67500 has good drug-like pharmacokinetic properties with a low first-pass effect and high bioavailability for an oral therapeutic agent of diabetes and osteoporosis.

• 대한한방부인과학회지
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• 제25권1호
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• pp.1-10
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• 2012

Purpose: This study was conducted to evaluate the inhibitory effect of Achyranthis Radix extract(ARE) loaded hydrogel on osteoclast differentiation. Methods: MTT-assay was performed to estimate cytotoxicity of ARE, Achyranthis Radix-alginate hydrogel disk(ARHD) in bone marrow macrophages stimulated(BMMs) with human receptor activator of nuclear factor-${\kappa}B$ ligand(RANKL), human macrophage-colony stimulating factor(M-CSF). Tartrate resistant acid phosphatase staining and RT-PCR were performed to know the inhibitory effect on osteoclast differentiation. Reactive oxygen species and actin ring formation were analysed to observe the effect of ARHD. Results: ARE has no cytotoxicity at the concentration of 0.1 $mg/m{\ell}$ or lower. ARE decreased the number of TRAP positive cells in RANKL, M-CSF stimulated BMMs and the gene expression. ARHD has no cytotoxicity at the concentration of 10 ${\mu}g/m{\ell}$ (24, 48hours), 50 ${\mu}g/m{\ell}$ (24 hours). ARHD restrained the synthesis of reactive oxygen species and the formation of actin ring. Conclusions: Achyranthis Radix has the inhibitory effect of osteoclast differentiation and bone resorption. Further studies are needed to treat osteoporosis by Achyranthis Radix.

• 대한한방부인과학회지
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• 제27권1호
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• pp.17-27
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• 2014

Objectives: This study was conducted to evaluate the inhibitory effect of polygoni cuspidati radix (PCR) extract on osteoclast differentiation. Methods: MTT-assay was performed to estimate cytotoxicity of PCR extract in BMMs stimulated with RANKL. Tartrate resistant acid phosphatase (TRAP) staining, TRAP activity and RT-PCR were performed to know the inhibitory effect on osteoclast differentiation. actin ring formation were analysed to observe the effect of PCR extract. Results: PCR decreased the number of TRAP positive cells and TRAP activities in BMMs stimulated with RANKL and M-CSF. PCR restrained the formation of actin ring. PCR down regulated the induction of NFATc1, c-Fos, TRAP and OSCAR by RANKL. PCR inhibited NF-${\kappa}B$ activity by inducing degradation of $I{\kappa}B{\alpha}$. Conclusions: We suggest that PCR Extracts can be an effective therapeutic agent on osteoclast differentiation caused by diseases such as osteoporosis.

• Nutrition Research and Practice
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• 제15권5호
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• pp.579-590
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• 2021

BACKGROUND/OBJECTIVES: Petasites japonicus Maxim (P. japonicus) has been used as an edible and medicinal plant and contains many bioactive compounds. The purpose of this study is to investigate the effect of P. japonicus on osteogenesis. MATERIALS/METHODS: The leaves and stems of P. japonicus were separated and extracted with hot water or ethanol, respectively. The total phenolic compound and total polyphenol contents of each extract were measured, and alkaline phosphatase (ALP) activity of each extract was evaluated to determine their effect on bone metabolism. To investigate the effect on osteoblast differentiation of the aqueous extract of P. japonicus leaves (AL), which produced the highest ALP activity among the tested extracts, collagen content was measured using the Sirius Red staining method, mineralization using the Alizarin Red S staining method, and osteocalcin production through enzyme-linked immunosorbent assay analysis. Also, real-time reverse transcription polymerase chain reaction was performed to investigate the mRNA expression levels of Runt-related transcriptional factor 2 (Runx2) and Osterix. RESULTS: Among the 4 P. japonicus extracts, AL had the highest values in all of the following measures: total phenolic compounds, total polyphenols, and ALP activity, which is a major biomarker of osteoblast differentiation. The AL-treated MC3T3-E1 cells showed significant increases in induced osteoblast differentiation, collagen synthesis, mineralization, and osteocalcin production. In addition, mRNA expressions of Runx2 and Osterix, transcription factors that regulate osteoblast differentiation, were significantly increased. CONCLUSIONS: These results suggest that AL can regulate osteoblasts differentiation, at least in part through Runx2 and Osterix. Therefore, it is highly likely that P. japonicus will be useful as an alternate therapeutic for the prevention and treatment of osteoporosis.

• 한국식생활문화학회지
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• 제36권6호
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• pp.595-606
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• 2021

Unhealthy dietary behavior such as insufficient calcium intake can be one of risk factors of osteoporosis and chronic diseases in older people. This study evaluated the recent trends in dietary calcium intake and the food source in Korean adults aged 50 years or older using the Korea National Health and Nutrition Examination Survey (KNHANES, 2015-2019) data. This study used 24-hour recall survey data to investigate the calcium intake, the major food groups and main dishes contributing to the calcium intake. The mean calcium intake was 479.55-506.81 mg/day. The major food groups that contribute to calcium intake were vegetables, milks and fishes. Dairy and frozen desserts and kimchi were the major dish groups that contributed to the calcium intake. Calcium intake from milk in dairy and frozen dessert group has been high in last 5 years (50-64 years old: 34.71-47.68 mg, 65-74 years old: 29.72-43.65 mg, over 75 years old: 22.91-42.93 mg). In addition, baechu-kimchi is the most contributed to the calcium intake in kimchi group (50-64 years old: 35.10-41.47 mg, 65-74 years old: 29.62-34.96 mg, over 75 years old: 23.79-29.13 mg). In conclusion, various source of calcium needs to be recommended to increase intake calcium in over 50 years, which may reduce chronic diseases and improve quality of life.

• 대한한방내과학회지
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• 제39권6호
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• pp.1181-1190
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• 2018

Objective: This study investigated the effect of purified medical herb extracts such as Alisma canaliculatum and Polyporus umbellatuson adipogenic differentiation of human bone marrow derived mesenchymal stromal stem cells (hBMSCs). Methods: Two different medical herb were extracted using hot distilled water. The optimal concentration of extracts were fixed at 100 ng/ml by means of cell viability and cytotoxic assay. To test the adipogenic differentiation ability of extracts, we induced the adipogenesis of hBMSCs for 21 days. At day 5, the cell was harvested to check mRNA and protein expression level of adipogenic related factors. The efficacy of lipid droplet formation was evaluated using the oil-red O staining method at days 21. Results: Two different medical herb extracts have no toxicity on hBMSCs. And two different medical herb extracts significantly decreased formation of lipid droplet compared with control groups in hBMSCs. The A. canaliculatum extract group showed the lowest mRNA and protein expression level of adipossgenic related transcription factors. This data suggests that extract of A. canaliculatum and P. umbellata decrease the adipogenic differentiation of hBMSCs. Conclusions: Our findings indicate that water-extract of A. canaliculatum and P. umbellata will be useful therapeutic reagents for prevention of obesity related disease such as diabetes, hyperlipidemia, coronary artery disease, and osteoporosis.

• Journal of Dental Anesthesia and Pain Medicine
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• 제19권2호
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• pp.91-99
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• 2019

Background: The imbalance between osteoblasts and osteoclasts can lead to pathological conditions such as osteoporosis. It has been reported that opioid adversely affect the skeletal system, but it is inconsistent. Remifentanil is currently used as an adjuvant analgesic drug in general anesthesia and sedation. The aim of the present study was to investigate the effect of remifentanil on the osteoblast differentiation and mechanism involved in this effect. Methods: The C2C12 cells (mouse pluripotent mesenchymal cell line) were used as preosteoblast. Osteoblastic differentiation potency was determined by alkaline phosphatase (ALP) staining. C2C12 cell migration by remifentanil was evaluated using Boyden chamber migration assay. The expression of Runx2 and osterix was evaluated by RT-PCT and western blot analysis to investigate the mechanism involved in remifentanil-mediated osteoblast differentiation. Results: ALP staining showed that remifentanil increased significantly osteoblast differentiation. In Boyden chamber migration assay, C2C12 cell migration was increased by remifentanil. RT-PCR and western blot analysis showed that the expression of Runx2 and osterix was upregulated by remifentanil. Conclusions: We demonstrated that remifentanil increased osteoblast differentiation in vitro by upregulation of Runx2 and osterix expression. Therefore, remifentanil has the potential for assisting with bone formation and bone healing.

• 대한골대사학회지
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• 제25권4호
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• pp.227-233
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• 2018

Background: Few studies have investigated the effects of sarcopenia on postoperative outcomes including mortality rates following surgery for osteoporotic hip fractures. The purpose of the present study was to determine the prevalence of sarcopenia and the relationship between sarcopenia and 1- and 5-year mortality rates in a consecutive series of patients with osteoporotic hip fractures. Methods: Among patients who underwent hip surgery for osteoporotic hip fractures, this study included 91 patients subjected to abdominal computed tomography within 1 year of hip surgery. We defined sarcopenia using sex-specific cut-off points for the skeletal muscle index at the level of the third lumbar vertebra. All patients were divided into 2 groups according to the presence or absence of sarcopenia and the 1- and 5-year mortality rates were compared. To confirm factors affecting mortality in addition to sarcopenia, we examined patient age, sex, American Society of Anesthesiologists grade, location of fracture, type of surgery, and bone mineral density. Results: The 1- and 5-year mortality rates were 20.9% and 67.2%, respectively. Among the 45 patients with sarcopenia, the 1- and 5-year mortality rates were 22.2% and 82.7%, respectively. Of the 46 patients without sarcopenia, the 1- and 5-year mortality rates were 19.6% and 52.7%, respectively. Results of the Kaplan-Meier analysis showed that sarcopenia did not affect the 1-year mortality rate (P=0.793), but had a significant effect on the 5-year mortality rate (P=0.028). Both perioperative sarcopenia (P=0.018) and osteoporosis (P=0.000) affected the 5-year mortality rate. Conclusions: Sarcopenia increases the risk of 5-year mortality in patients with osteoporotic hip fractures.

• Clinics in Shoulder and Elbow
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• 제21권4호
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• pp.220-226
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• 2018

Background: This study introduces a surgical technique with good clinical outcome useful in the treatment of osteoporotic displaced 3- or 4-part proximal humeral fractures. Methods: From May 2014 to February 2016, 16 patients with displaced 3- or 4-part proximal humeral fractures were treated by application of a locking plate with an endosteal strut allograft via a deltoid splitting approach with a minimum follow-up of 12 months. The allograft was inserted through a fractured gap of the greater tuberosity to support the humeral head and then fixed by a locking plate with meticulous soft tissue dissection to protect the axillary nerve. Surgical outcomes were evaluated by the American Shoulder and Elbow Surgeons (ASES) and visual analogue scale (VAS) scores, radiological imaging, and clinical examination. Fixation failure on radiographs was defined as a >$5^{\circ}$ loss of neck shaft angle (NSA) compared to that on an immediate postoperative radiograph. Avascular necrosis (AVN) of the humeral head was also evaluated. Results: In all cases, complete union was achieved. The ASES and VAS scores were improved to $85.4{\pm}2.1$ and $3.2{\pm}1.3$, respectively. Twelve patients (75.0%) had greater than a $5^{\circ}$ change in NSA; the average NSA change was $3.8^{\circ}$. Five patients (31.3%) had unsatisfactory ranges of motion exhibiting a <$100^{\circ}$ active forward flexion. No axillary nerve injuries or AVN were observed at the last follow-up. One patient was converted to reverse total arthroplasty due to severe pain and functional deficit. Conclusions: Minimally invasive fixation via a locking compression plate and an endosteal fibula strut allograft in Neer classification 3-or 4-part fractures with severe osteoporosis in elderly patients can achieve good clinical results.