• CELLMED
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• v.8 no.3
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• pp.13.1-13.8
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• 2018

In the field of osteoporosis, there has been growing interest in anabolic agents that enhance bone formation. The purpose of this study was to examine the effects of NNMBS 246 osteoblastic differentiation with associated signaling pathways. NNMBS 246 markedly increased alkaline phosphatase (ALP) activity and calcium nodule formation. Stimulation with NNMBS 246 not only increased the differentiation markers (ALP, OPN, OCN) level and transcription markers (RUNX2, Osterix) mRNA expression but also upregulated the ECM molecules and OPG mRNA expression. Treatments of NNMBS 246 downregulated MMPs (MMP-1, MMP-2, MMP-9), but RANKL mRNA expression. Furthermore, NNMBS 246 activated osteoblastic differentiation markers and formed calcium nodules in human periodontal ligament cells (hPDLCs) and cementoblast cells. NNMBS 246 induced phosphorylation of MAPKs, Akt, nuclear p65 and IkB-${\alpha}$. BMP-2/Smad and ${\beta}$-catenin signaling pathways were activated by NNMBS 246. Sirtinol (SIRT1 inhibitor) inhibited NNMBS 246-induced osteoblastic differentiation markers mRNA expression. These results suggested that NNMBS 246 has the potential to enhance osteoblastogenesis probably through the activation of BMP/Smad and ${\beta}$-catenin signal pathways, and SIRT1 plays as critical mediator in bone anabolic effect of NNMBS 246.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.9
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• pp.4331-4334
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• 2012

Aim and Background: The aim of the present study was to evaluate correlations between serum osteocalcin, osteoprotegerin and NTX (Cross-linked N-telopeptides of Type I Collagen) and urinary NTX in breast and lung cancer patients with bone metastases. These four markers are considered to have important roles in bone formation, resorption and metastases. Methods: Four markers were determined in the sera of 60 breast cancer and 21 lung cancer patients and healthy controls (n=30). Serum levels were studied using ELISA and EIA. Results: The median levels of serum osteoprotegerin (p<0.001) and osteocalcin (p=0.003) were higher in patients. Significant correlations were observed between the serum NTX-osteocalcin (r=0.431; p<0.001), serum NTX-osteoprotegerin (r=0.42; p=0.003) and serum NTX - urine NTX (r=0.255; p=0.022). Conclusion: We conclude that osteocalcin, osteoprotegerin and NTX are independent diagnostic tools. Due to the ease of urine collection, urine NTX may be applied routinely to allow early detection of bone metastases and indicate progression of the disease.

• Journal of Korean Neurosurgical Society
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• v.51 no.6
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• pp.323-327
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• 2012

Objective : The purpose of this study was to verify the appropriateness of ovariectomized rats as the osteoporosis animal model. Methods : Twelve female Sprague-Dawley rats underwent a sham operation (the sham group) or bilateral ovariectomy [the ovariectomy (OVX) group]. Eight weeks after operations, serum biochemical markers of bone turnover were analyzed; osteocalcin and alkaline phosphatase, which are sensitive biochemical markers of bone formation, and C-terminal telopeptide fragment of type I collagen C-terminus (CTX), which is a sensitive biochemical marker of bone resorption. Bone histomorphometric parameters and microarchitectural properties of 4th lumbar vertebrae were determined by micro-computed tomographic (CT) scan. Results : The OVX group showed on average 75.4% higher osteocalcin and 72.5% higher CTX levels than the sham group, indicating increased bone turnover. Micro-CT analysis showed significantly lower bone mineral density (BMD) (p=0.005) and cortical BMD (p=0.021) in the OVX group. Furthermore, the OVX group was found to have a significantly lower trabecular bone volume fraction (p=0.002). Conclusion : Our results showed that bone turnover was significantly increased and bone mass was significantly decreased 8 weeks after ovariectomy in rats. Thus, we propose that the ovariectomized rat model be considered a reproducible and reliable model of osteoporosis.

• Nutrition Research and Practice
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• v.4 no.6
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• pp.507-514
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• 2010

Vitamin K intake has been reported as an essential factor for bone formation. The current study was conducted under the hypothesis that insufficient vitamin K intake would affect inflammatory markers and bone mineral density in young adult women. The study was a cross-sectional design that included 75 women in their 20s. Physical assessments, bone mineral density measurements, 24-hr dietary recalls, and biochemical assessments for high sensitivity C-reactive protein (hs-CRP) and percentages of undercarboxylated osteocalcin (%ucOC) were performed. An analysis of vitamin K nutritional status was performed comparing first, second, and third tertiles of intake based on %ucOC in plasma. Vitamin K intake levels in the first, second, and third tertiles were $94.88{\pm}51.48\;{\mu}g$, $73.85{\pm}45.15\;{\mu}g$, and $62.58{\pm}39.92\;{\mu}g$, respectively (P < 0.05). The T-scores of the first and third tertiles were 1.06 and -0.03, respectively, indicating that bone mineral density was significantly lower in the group with lower vitamin K intake (P < 0.05). There was a tendency for different serum hs-CRP concentrations between the first ($0.04{\pm}0.02$) and third tertiles ($0.11{\pm}0.18$), however this was not statistically significant. Regression analysis was performed to identify the correlations between vitamin K nutritional status, inflammatory markers, and bone mineral density after adjusting for age and BMI. Serum hs-CRP concentrations were positively correlated with vitamin K deficiency status (P < 0.05). And bone mineral density, which was represented by speed, was negatively correlated with vitamin K deficiency status (P < 0.05). In conclusion, status of vitamin K affects inflammatory status and bone formation. Therefore, sufficient intake of vitamin K is required to secure peak bone mass in young adult women.

• Journal of Nutrition and Health
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• v.42 no.4
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• pp.309-317
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• 2009

As far as we know, there were no studies of the effect of L-arginine on bone metabolism in post-menopausal women or ovariectomized rats. The primary objective of the current study was to determine whether arginine supplementation was associated with alterations in femoral and spinal bone mineral density (BMD) and bone markers in ovariectomized (Ovx) rats. Forty female Sprague-Dawley rats were divided into two groups, Ovx and sham groups, which were each randomly divided into two subgroups that were fed control and arginine supplemented diet. All rats were fed on experimental diet and deionized water ad libitum for 9 weeks. Bone formation was measured by serum osteocalcin and alkaline phosphatase (ALP) concentrations. Bone resorption was measured by deoxypyridinoline (DPD) crosslinks immunoassay and corrected for creatinine. Serum osteocalcin, growth hormone, insulin-like growth factor-1 (IGF-1), parathyroid hormone (PTH) and calcitonin were analyzed using radioimmunoassay kits. Bone mineral density (BMD) and bone mineral content (BMC) were measured using PIXImus (GE Lunar Co, Wisconsin, USA) in spine and femur. The serum and urine concentrations of Ca and P were determined. The plasma was analyzed for arginine. Diet did not affect weight gain, mean food intake, and plasma arginine concentration. Urinary Ca excretion was decreased by arginine supplementation in Ovx rats, but statistically not significant. The Ovx rats fed arginine-supplemented diet were not significantly different in ALP, osteocalcin, crosslinks value, PTH, calcitonin and IGF-1 compared to those fed control diet. The arginine-supplemented group had significantly higher serum Ca and growth hormone than control group. Spine and femur BMD were significantly increased by arginine supplementation on 5th and 9th weeks after feeding. Our findings indicate that dietary L-arginine supplementation decreased bone mineral density loss in Ovx rats. Therefore, dietary arginine supplementation may represent a potentially useful strategy for the management of osteoporosis.

• Journal of Nutrition and Health
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• v.44 no.3
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• pp.189-195
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• 2011

Vitamin K has been suggested to plays a role in bone metabolism. The objective of this study was to determine whether vitamin K2 supplementation is related to bone mineral density, bone formation markers, and bone resorption in ovariectomized (OVX) rats. Forty Sprague-Dawley female rats (body weight, $200{\pm}10$ g) were divided into four groups: a sham group fed a control diet, a sham group fed a vitamin K2 supplemented diet, OVX fed a control diet, and OVX fed a vitamin $K_2$ supplemented diet (3.5 mg vitamin $K_2$/kg diet). All rats were fed the experimental diets for 6 weeks, and deionized water was provided ad libitum. Serum alkaline phosphatase activity (ALP), osteocalcin, and urinary deoxypyridinoline crosslink values were measured as markers of bone formation and resorption. Bone mineral density (BMD) and bone mineral content were measured in the spine and femur using PIXImus (GE Lunar Co., Madison, WI, USA). No significant differences in body weight gain, food intake, or food efficiency ratio were observed between the control and experimental groups. Serum ALP, osteocalcin, and urinary crosslink values were not significantly different between the vitamin $K_2$ supplemented groups. No significant differences were observed for any of the variables in the sham group. Spine BMD values were significantly lower in the OVX than those in the sham groups. Spine and femur BMD per weight of vitamin $K_2$ tended to be higher than the control diet group within the OVX group, but no significant differences were observed. In conclusion, dietary vitamin $K_2$ supplementation may have a beneficial effect on spine and femur BMD in OVX rats. Further research is needed to understand the potential benefits of vitamin $K_2$ on bone loss in OVX rats.

• Journal of the Korea Academia-Industrial cooperation Society
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• v.10 no.12
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• pp.3943-3952
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• 2009

This study investigated the changes in bone mineral density(BMD) and biochemical bone turnover markers over 1 year in healthy young college women. In comparison of changes in BMD at the lumbar spine, proximal femur (trochanter, femoral neck, Ward's triangle), and whole body over 1 year, there was only a significant difference in that at forearm. However, serum osteocalcin, a marker of bone formation, and urinary deoxypyridinoline, a marker of bone reabsorption, were significantly changed over 1 year. These findings indicate that although BMD does not significantly change in early young adult, the changes of bone metabolism markers seem to mean active bone turnover in early young adult women.

• Journal of Veterinary Clinics
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• v.19 no.4
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• pp.405-410
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• 2002

The purpose of this investigation was to examine the effects of osteocalcin (serum bone GLA-protein, BGP) and procollagen carboxy-terminal propeptide (PICP) on new bone formation of canine fracture models. Serum osteocalcin and PICP were measured by standard RIA. The values of osteocalcin and PICP in the non-union and delayed-union fracture models were measured biweekly for 20 weeks in 14 dogs. The unions were radiographed for fracture healing. In non-union fracture group, the activity of BGP was markedly increased at four to eight weeks and decreased at twelve to twenty weeks and the activity of PICP was markedly increased at two to six weeks and slightly decreased at sixteen to twenty weeks. In delayed-union fracture group, the activity of BGP was markedly increased at two to eight weeks after treatment and maintained for the level until twenty weeks and the activity of PICP was markedly increased at two to six weeks after treatment and maintained for the level until twenty weeks. Radiologically, non-union group was not achieved until twenty weeks after fracture, delayed-union group was successfully achieved in eighteen weeks after fracture. These results suggested that the. activities of osteocalcin and PICP are useful parameters for biochemical markers of bone formation in dogs.

• The korean journal of orthodontics
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• v.31 no.3 s.86
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• pp.357-367
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• 2001

The purpose of this study was to investigate the alveolar bone turnover in diabetic rat, and to compare the alveolar bone turnover during tooth movement in diabetes with that in normal control Eighty Male Sprague-Dawley strain rats(8th week) were divided into normal control(N), normal-tooth movement (N-tm), diabetes(D), and diabetes-tooth movement(D-tm) groups. Eighteen days before the start of the experiment, diabetes was induced with a single injection of streptozotocin 50 mg/kg of body weight in citrate buffer as vehicle via the tail vein. Maxillary first molars of rats were moved mesially by 40 grams of the closed coil spring. Experimental animals were sacrificed after 1d, 3d, 7d, and 14d experimental period, and the alveolar bone around the maxillary first molars were assayed biochemically for acid phsophatase(ACP) and tartrate-resistant acid phosphatase (TRAP) as bone resorption markers, and alkaline phosphatase(ALP) and osteocalcin(OC) as bone formation markers. TRAP and OC concentration in serum and alveolar bone of D group were lower than those in N group, and especially OC concentration decreased mote following diabetes prolonged, which showed the decreased skeletal and alveolar bone resorption and formation potential in diabetic rats. In N-tm group compared with N group, alveolar bone ACP and TRAP concentrations were highest at 1d and 3d(p<0.01), decreased after then, and showed lowest at 14d, and alveolar bone OC concentration was higher at 3d, 7d, and 14d(p<0.001) and showed a tendency of peak level at 7d. which showed the peak of concentration of bone resorption markets at 1d-3d and those of bone formation markers at 7d. In D-tm group compared with N group, alveolar bone ACP and TRAP concentrations were higher at 3d, 7d and 14d(p<0.001), and tended to reach peak value at 7d and persisted through 14d, and alveolar bone ALP and OC concentration increased but not different from that of N group. The amount of tooth movement in D group were greater than that of N group at all experimental period. Those results were suggested that during diabetes, the alveolar and skeletal bone undergo low bone turnover and the mote amount of tooth movement, hut because the peak time of alveolar bone resorption activity was delayed and sustained in longer period of tooth movement and alveolar bone formation activity is lower than that of normal tooth movement, the periodontal space is supposed to be larger doting tooth movement.

• Journal of Trauma and Injury
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• v.18 no.2
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• pp.87-93
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• 2005

Background: The most frequent fracture seen at the emergency department (ED) in the elderly is a femur fracture whereas they do not know the degree of osteoporosis. We analyzed the degree of osteoporosis in patients with femur fractures and compared patients with only femur fractures (FX) to patients with femur and vertebral fractures (VX) by examining the clinical features, the bone mineral density (BMD), and biochemical markers. Methods: From January 2004 to December 2004, we enrolled prospectively 30 femur fracture patients who visited the ED. The bone mineral densities of the lumbar spine and the femur were examined. Total calcium, phosphate, alkaline phosphatase, osteocalcin, and serum C-terminal telopeptide (s-CTx) were measured. The patients with femur fractures were divided into two subgroups according to the presence of vertebral fracture. Results: All BMDs of the FX group showed osteoporosis. The s-CTx levels were higher than normal. The patients in the FX with VX were older than those in the FX only group, and had lower BMDs. There were no significant differences in markers between the subgroups, but the incidence of trochanteric fractures was higher in FX with VX group than in the FX only group. Conclusion: Femur fractures in the elderly were associated with osteoporosis. In our study, despite a considerable difference in BMD between patients with femur fractures and those with femur fractures combined with vertebral fractures, there was no difference in biochemical markers on bone formation nor in the those of bone resorption. We will further investigate the biochemical markers and BMD in the population of osteoporotic fractures. So those indicators should be helpful for planning treatment and for prevention of FX in the elderly.