• Journal of Korean Neurosurgical Society
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• v.64 no.4
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• pp.486-494
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• 2021

The growth of pulsed electromagnetic field (PEMF) therapy and its progress over the years for use in post-operative bone growth has been revolutionary in its effect on bone tissue proliferation and vascular flow. However, further progress in PEMF therapy has been difficult due to lack of more evidence-based understanding of its mechanism of action. Our objective was to review the current understanding of bone growth physiology, the mechanism of PEMF therapy action along with its application in spinal surgery and associated outcomes. The authors of this review examined multiple controlled, comparative, and cohort studies to compare fusion rates of patients undergoing PEMF stimulation. Examining spinal fusion rates, a rounded comparison of post-fusion outcomes with and without bone stimulator was performed. Results showed that postoperative spinal surgery PEMF stimulation had higher rates of fusion than control groups. Though PEMF therapy was proven more effective, multiple factors contributed to difficulty in patient compliance for use. Extended timeframe of treatment and cost of treatment were the main obstacles to full compliance. This review showed that PEMF therapy presented an increased rate of recovery in patients, supporting the use of these devices as an effective post-surgical aid. Given the recent advances in the development of PEMF devices, affordability and access will be much easier suited to the patient population, allowing for more readily available treatment options.

• Asian Spine Journal
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• v.12 no.6
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• pp.973-980
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• 2018

Study Design: Retrospective review. Purpose: To identify the trends in stimulator use, pair those trends with various grafting materials, and determine the influence of stimulators on the risk of revision surgery. Overview of Literature: A large number of studies has reported beneficial effects of electromagnetic energy in healing long bone fractures. However, there are few clinical studies regarding the use of electrical stimulators in spinal fusion. Methods: We used insurance billing codes to identify patients with lumbar disc degeneration who underwent anterior lumbar interbody fusion (ALIF). Comparisons between patients who did and did not receive electrical stimulators following surgery were performed using logistic regression analysis, chi-square test, and odds ratio (OR) analysis. Results: Approximately 19% of the patients (495/2,613) received external stimulators following ALIF surgery. There was a slight increase in stimulator use from 2008 to 2014 (multi-level $R^2=0.08$, single-level $R^2=0.05$). Patients who underwent multi-level procedures were more likely to receive stimulators than patients who underwent single-level procedures (p<0.05; OR, 3.72; 95% confidence interval, 3.02-4.57). Grafting options associated with most frequent stimulator use were bone marrow aspirates (BMA) plus autograft or allograft for single-level and allograft alone for multi-level procedures. In both cohorts, patients treated with bone morphogenetic proteins were least likely to receive electrical stimulators (p<0.05). Patients who received stimulation generally had higher reimbursements. Concurrent posterior lumbar fusion (PLF) (ALIF+PLF) increased the likelihood of receiving stimulators (p<0.05). Patients who received electrical stimulators had similar revision rates as those who did not receive stimulation (p>0.05), except those in the multilevel ALIF+PLF cohort, wherein the patients who underwent stimulation had higher rates of revision surgery. Conclusions: Concurrent PLF or multi-level procedures increased patients' likelihood of receiving stimulators, however, the presence of comorbidities did not. Patients who received BMA plus autograft or allograft were more likely to receive stimulation. Patients with and without bone stimulators had similar rates of revision surgery.

• Journal of the Korean Society for Precision Engineering
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• v.29 no.5
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• pp.578-583
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• 2012

The pharmacological therapies and whole body vibration as non-pharmacological therapies were known to have adverse side effects. Therefore, partial stimulation was suggested and its effects were evaluated. This study aimed to evaluate the site-specific effects of partial stimulator for treatment of osteoporosis induced by estrogen deficiency. Sixteen virginal Sprague-Dawley rats (12 weeks old) were divided into 2 groups(no stimulation, stimulation groups). All rats were ovariectomised to induce osteoporosis. After 3 weeks of operation, the right tibiae in rats of stimulation group (frequency: 10Hz, cycle: 1500, strain on bone surface: $2000{\mu}{\varepsilon}$) were stimulated perpendicularly at right tibia by using partial stimulator for 6 weeks (3days/week). The right tibiae in rats were scanned, before stimulation (0 week) and at 6 weeks after stimulation by using in-vivo micro computed tomography. For investigation of changes in morphological characteristics, structural parameters were measured and calculated. At 6 weeks the morphological characteristics (relative value) in stimulation group were significantly enhanced than those in no stimulation group (p<0.05). In this study, we find that after 6 weeks of partial stimulation, the morphological characteristics of tibia trabecular bone were enhanced. Thus, we concluded that partial stimulation could be used to treat osteoporosis.

• The Korea Journal of Herbology
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• v.32 no.1
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• pp.69-74
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• 2017

Objectives : This study aimed to investigate the effects of Angelicae sinensis Radix on longitudinal bone growth rate in rats. We have screened traditional medicinal herbs to develop the longitudinal bone growth stimulator by well-established rat model. A. sinensis was identified as one of the effective herbs in the screening process. Methods : Adolescent female rats were administered A. sinensis at doses of 30 mg/kg and 300 mg/kg for 10 consecutive days. To observe the rate of longitudinal bone growth, tetracycline was injected intraperitoneally on day 8 to stain a fluorescent band on the anew formed bone. To elucidate the mode of action, we observed insulin-like growth factor-1 (IGF-1) and bone morphogenetic protein-2 (BMP-2) expression after A. sinensis administration in growth plate. Results : In the 300 mg/kg A. sinensis group, the length between the proximal endpoint of the tetracycline label and the division line between growth plate and bone was significantly increased compared with vehicle-treated control group. Height of the proximal tibial growth plate was higher in the A. sinensis group compared with control group. A. sinensis also upregulated the expressions of IGF-1 and BMP-2 in the proliferative zone and hypertrophic zone of the proximal tibial growth plate. Conclusions : A. sinensis increases longitudinal bone growth rate in rats. According to immunohistochemistry, A. sinensis increases local IGF-1 and BMP-2 expressions in the growth plate which can be considered as direct stimulation of GH on the local growth plate.

• Journal of Yeungnam Medical Science
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• v.25 no.1
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• pp.19-30
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• 2008

Osteoporosis, a disease characterized by low bone mass and microarchitectural deterioration of bone tissue leading to enhanced bone fragility and fracture risk, is a major public health problem. The diagnostic methods for osteoporosis include simple radiography, bone scan, DXA (Dual energy X-ray Absortiometry) and biochemical markers of bone turnover. Optimal treatment and prevention of osteoporosis require modification of risk factors, particularly smoking cessation, adequate physical activity, and attention to diet, in addition to pharmacologic intervention. The estrogens and raloxifene both prevent bone loss in postmenopausal women, and the estrogens probably also decrease the risk of first fracture. There is good evidence that raloxifene prevents further fractures in postmenopausal women who already have had fractures and some evidence that estrogen does as well. Bisphosphonate prevents bone loss and reduces fractures in healthy and osteoporotic postmenopausal women and in osteoporotic men as well. Risedronate is more potent and has fewer side effects than alendronate and reduces the incidence of fractures in osteoporotic women. Calcitonin increases bone mineral density in early postmenopausal women and men with idiopathic osteoporosis, and also reduces the risk of new fractures in osteoporotic women. All of the agents discussed above prevent bone resorption, whereas teriparatide and strontium increase bone formation and are effective in the treatment of osteoporotic women and men. New avenues for targeting osteoporosis will emerge as our knowledge of the regulatory mechanisms of bone remodeling increases, although issues of tissue specificity may remain to be addressed.

• Transactions of the Korean Society of Mechanical Engineers A
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• v.33 no.7
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• pp.629-636
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• 2009

Mechanical stimulation is known to play a vital role on the differentiation of mesenchymal stem cells (MSCs) to pre-osteoblasts. In this research, we developed a tensile cell stimulator, composed of a DC motor-driven actuator and LVDT sensor for measuring linear displacement, to study the effects of tensile stress on osteogenic differentiation of MSCs. First, we demonstrated the reliability of this device by showing the uniform strain field in the silicon substrate. Secondly, we investigated the effects of tensile stretching on osteogenic differentiation. We imposed a pre-set cyclic strain at a fixed frequency on cell monolayer cultured on a flexible silicon substrate while varying its amplitude and duration. 60 min of resting period was allowed between 30 min of cyclic stretching and this cycle is repeated up to 7 days. Under the combined stimulation with osteogenic media and mechanical stretching, the osteogenic markers such as alkaline phosphatase (ALP), osterix, and osteopontin began to get expressed as early as 4 days of stimulation, which is much shorter than what is typically required for osteogenic media induced differentiation. Moreover, different markers were induced at different magnitudes of the applied strains. Lastly, for the case of ALP, we observed the antagonistic effects of osteogenic media when combined with mechanical stretching.

• The korean journal of orthodontics
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• v.25 no.6 s.53
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• pp.715-722
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• 1995

Orthodontic tooth movement in response to orthodontic force results from actions of osteoclasts and osteeoblasts in the cell level. Convincing evidence has now been provided to support the view that osteoclasts are derived from mononuclear cells that originate in the bone marrow or other hematopoietic organs and they migrate to the bones via vascular routes. Nitric oxide(NO), which accounts for the biological properties of endothelium-derived relaxing factor(EDRF), is the endogenous stimulator of soluble guanylate cylase. The discovery of the formation of nitric oxide(NO) from L-arginine in mammalian tissues and its biological roles has, in the last 7 years, thrown new light onto many areas of research. Data from experiments in vitro showed that N-metyl-L-arginine(L-NMA) and L-nitro-L- arginine(L-NAME) are competitive inhibitors of nitric oxide synthase. This study suggest that the multinucleated cells in our culture have characteristics of osteoclasts and that the potential bone cell activity of nitric oxide in vitro may be mediated in part by stimulation of marrow mononuclear cells to form osteoclast-like cells. Bone marrow cells were obtaineed from tibia of 19-days old chick embryo. After sacrifice, tibia was quickly dissected and the bone were then split to expose the medullary bone. The cells were attached for 4 hours and the nonadherent cells were collected. Marrow cells weere cultured in 96-well plate in medium 199. To examine the number of TRAP-positive multinucleated cells(MNCs), $10^{-8}\;M\;Vit=D_3$ and various concentration of L-NMA and L-NAME weere added at the beginning of cultures and with each medium change. After 7 days of culture. tartrate-resistant acid phosphatase(TRAP) staining was performed for microscopic evaluation. Cells haying more than three nuclei per cell were counted as MNCs. The obsrved results were as follows;1. 1,25-dihydroxyvitamine $D_3$ stimulated the osteoclast-like multinucleated cells in cultures of chick embryo bone marrow. 2. Nitric oxide synthase inhibitors(NOSI ; N-NMA, N-NAME) stimulated the osteoclast-like cells in cultures of chick embry bone marrow. 3. 1,25-dihydroxyvitamine$D_3$ and nitric oxide synthase inhibitors did not appear to have additive effect on the generation of TRAP-positive MNCs. These results suggest that nitric oxide synthase inhibitors may stimulate the osteoclast-like multinucleated cell formation and fusion in cultures of chick bone marrow.

• Proceedings of the Korea Contents Association Conference
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• 2009.05a
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• pp.1124-1129
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• 2009

This study aims to examine the effects of non-invasive constant microcurrent stimulation on expression of Bone Morphogenetic Protein(BMP) 4 after tibia fracture in rabbits. Twenty four rabbits with tibia fracture were randomly divided into control and experimental groups. Each group was divided into four subgroups, based on the duration of the experiment (3, 7, 14, 28 days). The experimental groups received a constant microcurrent stimulation of $20{\sim}25{\mu}A$ intensity with surface Ag-AgCl electrode (diameter 1cm, Biopac, U.S.A.) for 24 hours a day. Cathode of the microcurrent stimulator located on the tibia directly, anode of it did on the gastrocnemius muscle. Rabbits were sacrificed on each of the postoperative days 3, 7, 14, 28. To investigate how non- invasive constant microcurrent stimulation affects bone healing, immunohistochemical analysis of BMP-4 was performed at each point. After evaluation, the test results are as follows: Comparisons of immunohistochemical observation of BMP-4 in 7 days after tibial fracture show that there was shown to be a moderate positive reaction (++) on concentric circles of Harversian system andt he interstitial lamella in the control group, while there was a very strong positive reaction (++++) on concentric circles of Harversian system and interstitial lamellain the experimental group. These results suggest that applying non-invasive constant microcurrent stimulation on fractured bone is helpful to bone healing.

• Journal of Microbiology
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• v.45 no.6
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• pp.566-571
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• 2007

Bacterial lipopolysaccharide (LPS) is a potent stimulator of bone resorption in periodontitis. Co-culture systems of mouse calvaria-derived osteoblasts and bone marrow-derived preosteoclasts were used as an in vitro osteoclast differentiation. This study revealed that co-cultures using ddY or ICR mouse strain responded differently to LPS while responded equally to $1{\alpha},25(OH)_2D_3$. Thus, the different response to LPS indicates dissimilarity of two mouse stains in their capacity for generating osteoclasts while the two mouse strains share the similarity in response to $1{\alpha},25(OH)_2D_3$. To identify which cells between osteoblasts and preosteoclasts in the co-culture are responsible for the dissimilarity, the reciprocal co-cultures were performed between ddY and ICR mouse strains. The treatment of $1,25(OH)_2D_3$ to ddY/ICR (osteoblasts from ddY/preosteoclasts from ICR) and ICR/ddY reciprocal co-cultures also showed the similarity. In case of LPS treatment, the results of ddY/ICR were similar to ddY/ddY and the results of the other reciprocal co-culture, ICR/ddY combination, were consistent with those of ICR/ICR. It suggests that the dissimilarity between the two mouse strains may resident in osteoblasts but not in preosteoclasts. Therefore, the osteoblast is responsible for mouse strain-dependent osteoclastogenesis in response to LPS. Although mouse models will continue to provide insights into molecular mechanisms of osteoclastogenesis, caution should be exercised when using different mouse strains, especially ddY and ICR strains as models for osteoclast differentiation.

• Food Quality and Culture
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• v.2 no.2
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• pp.85-88
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• 2008

We have investigated the effects of cottonseed extract on the proliferation, differentiation and lipopolysaccharide (LPS)-induced production of local factors in murine clonal osteoblastic MC3T3-E1 cells. Ethanol extract of cotton seed ($4{\sim}63{\mu}g/mL$) significantly increased the proliferatin of MC3T3-E1 cells (p<0.05). Moreover, cottonseed extract ($10{\sim}50{\mu}g/mL$) caused a significant elevation of alkaline phosphatase (ALP) activity and collagen content in the cells. Lipopolysaccharide (LPS) is a potent stimulator of bone resorption in inflammatory diseases. We examined the effect of cottonseed extract on the LPS-induced production of tumor necrosis factor a (TNF-$\alpha$) and nitric oxide (NO) in MC3T3-E1 cells. Treatment with cottonseed extract ($10{\sim}50{\mu}g/mL$) decreased the $5{\mu}g/mL$ LPS-induced production of TNF-$\alpha$ and NO in osteoblasts, suggesting that the antiresorptive action of cottonseed extract may be mediated by decrease in these local factors. This study suggests that cottenseed may contribute to antiresorptive action against osteoblastic cells, resulting in a beneficial effect in promoting the function of osteoblastic cells.