• Molecules and Cells
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• v.40 no.6
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• pp.393-400
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• 2017

Type 2 diabetes mellitus (T2DM) is a chronic metabolic disease characterized by lack of insulin and high glucose levels. T2DM can cause bone loss and fracture, thus leading to diabetic osteoporosis. Promoting osteogenic differentiation of osteoblasts may effectively treat diabetic osteoporosis. We previously reported that Sirtuin 1 (Sirt1), a $NAD^+$-dependent deacetylase, promotes osteogenic differentiation through downregulation of peroxisome proliferator-activated receptor (PPAR) ${\gamma}$. We also found that miR-132 regulates osteogenic differentiation by downregulating Sirt1 in a $PPAR{\beta}/{\delta}$-dependent manner. The ligand-activated transcription factor, $PPAR{\alpha}$, is another isotype of the peroxisome proliferator-activated receptor family that helps maintain bone homeostasis and promot bone formation. Whether the regulatory role of $PPAR{\alpha}$ in osteogenic differentiation is mediated via Sirt1 remains unclear. In the present study, we aimed to determine this role and the underlying mechanism by using high glucose (HG) and free fatty acids (FFA) to mimic T2DM in MC3T3-E1 cells. The results showed that HG-FFA significantly inhibited expression of $PPAR{\alpha}$, Sirt1 and osteogenic differentiation, but these effects were markedly reversed by $PPAR{\alpha}$ overexpression. Moreover, siSirt1 attenuated the positive effects of $PPAR{\alpha}$ on osteogenic differentiation, suggesting that $PPAR{\alpha}$ promotes osteogenic differentiation in a Sirt1-dependent manner. Luciferase activity assay confirmed interactions between $PPAR{\alpha}$ and Sirt1. These findings indicate that $PPAR{\alpha}$ promotes osteogenic differentiation via the Sirt1-dependent signaling pathway.

• The Korean Journal of Physiology and Pharmacology
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• v.18 no.1
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• pp.1-14
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• 2014

During long standing hyperglycaemic state in diabetes mellitus, glucose forms covalent adducts with the plasma proteins through a non-enzymatic process known as glycation. Protein glycation and formation of advanced glycation end products (AGEs) play an important role in the pathogenesis of diabetic complications like retinopathy, nephropathy, neuropathy, cardiomyopathy along with some other diseases such as rheumatoid arthritis, osteoporosis and aging. Glycation of proteins interferes with their normal functions by disrupting molecular conformation, altering enzymatic activity, and interfering with receptor functioning. AGEs form intra- and extracellular cross linking not only with proteins, but with some other endogenous key molecules including lipids and nucleic acids to contribute in the development of diabetic complications. Recent studies suggest that AGEs interact with plasma membrane localized receptors for AGEs (RAGE) to alter intracellular signaling, gene expression, release of pro-inflammatory molecules and free radicals. The present review discusses the glycation of plasma proteins such as albumin, fibrinogen, globulins and collagen to form different types of AGEs. Furthermore, the role of AGEs in the pathogenesis of diabetic complications including retinopathy, cataract, neuropathy, nephropathy and cardiomyopathy is also discussed.

• Journal of the Korea Society of Computer and Information
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• v.26 no.8
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• pp.197-207
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• 2021

Relationship between bone mineral density (BMD) and type 2 diabetes is still inconsistent. Recently, many epidemiologic data show that fracture risk is increased in type 2 diabetic patients regardless of BMD status. In this study, we used nation-wide data from 2008 to 2011 Korea National Health and Nutrition Examination Survey (KNHANES) to analyze the BMD status in patients with type 2 diabetes compared to non-diabetics. We included subjects aged 50 years or older in men (N=2,959, 2,430 without diabetes, 529 with type 2 diabetes) and postmenopausal women (N=2,902, 2,479 without diabetes, 423 with type 2 diabetes). Subjects with history of medication for osteoporosis or with illness or malignancy affecting bone metabolism were excluded. Data of anthropometric measurements and demographic characteristics were collected by trained examiner. Serum was separated from peripheral venous blood samples obtained after 8 hours of fasting. BMD was measured at lumbar spine and femur using dual-energy X-ray absorptiometry (DXA). There was a significant positive association between lumbar spine BMD and type 2 diabetes after adjusting age, gender, body mass index, monthly house income, education level, physical activity, daily calcium intake and vitamin D concentration by multiple regression analysis in all subjects. In the subgroup analysis by gender, this association was maintained both in male and female after adjusting those confounding factors. However, femur BMD was not different between type 2 diabetic and non-diabetic subjects. In conclusion, lumbar spine BMD was significantly higher in type 2 diabetic patients aged 50 years or more in men and postmenopausal women compared to non-diabetic subjects.

• Biomolecules & Therapeutics
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• v.11 no.2
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• pp.81-84
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• 2003

Recently, diabetes has been found to be associated with osteoporosis. Specially in IDDM. In both type I and type II diabetes, glucose levels are elevated. Thus, a linkage between high glucose and osteoporosis can not be ruled out. In this study, an attempt has been made to observe the effect of high glucose on bone formation; osteoblast like UMR 106 cells were treated with high glucose (22 mM, 33 mM) for 1, 3 or 7 days. The high concentration of glucose inhibited markers. of bone formation activity such as alkaline phosphatase and collagen synthesis. In addition, reduction in the level of total cellular protein in response to high glucose was also observed. This study showed high glucose concentration could alter the bone metabolism leading to a defective bone formation and thus paving the linkage of such situation to diabetic complications.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.28 no.2
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• pp.95-102
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• 2002

DM is a systemic disease with many complications. One of them, diabetic osteopenia is important sequelae and many authors reported reduced bone mass in diabetic rats. However, in mandible, study has been rare because of its anatomical limits. So the objective of this study was to investigate bony change in mandible of diabetic rats. Thirty-two adult rats were used in this study. Half of them were male and female respectively. In sixteen rats, streptozotocin was injected intraperitoneally to induce DM and the serum glucose concentration was checked to ensure the induction of DM prior to the time of sacrifice. At 1, 2, 3, 4, 6, 8, 12, 16weeks, control group and diabetic group rats were sacrificed respectively. And then bone mineral density of mandibles and femurs of the rats was measured using dual energy X-ray absorptiometry(DEXA). In addition serum osteocalcin and urine deoxypyridinoline were measured as markers of bone formation and resoption respectively. Mandibular and femoral bone density in streptozotocin induced rats was decreased with significance statistically after 4 weeks from injection. In mandible, comparing with femur, bone density was moderately decreased. The alveolar bone in mandible was more decreased bone density than the whole body in the mandible From these results, bone mineral density decreased in uncontrolled diabetic group with time, and especially alveolar bone was more destructive in the mandible. So authors think that consideration of reduced bone mineral density is necessary in dental procedure.

• Proceedings of the PSK Conference
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• 2003.04a
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• pp.125.1-125.1
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• 2003

Diabetes is complex in nature but it gets further complicated in associating with number of other diseases like hypertension, ratinal disintegration, renal failure and many others. The latest addition to diabetic-complication is its association with bone degeneration disease:osteoporosis, which is a form of bone loss. In both the types of primary diabetes, the insulin dependent diabetes militus (IDDM) as well in insulin independent diabetes millitus (IIDM) the glucose metabolism is altered. (omitted)

• Journal of Korean Foot and Ankle Society
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• v.7 no.2
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• pp.258-262
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• 2003

Avulsion fracture of the calcaneal tuberosity is an uncommon injury. Usually it occurs from indirect trauma, and can be seen in old patients with osteoporosis or in patients with diabetic neuropathy. Follow-up studies showed healing of the fracture in most cases, but skeletal deformity may develop in some cases. Therefore we should take plain X-ray evaluations in diabetic patients with foot and ankle pain, even though there have been no definite trauma history. Four cases of calcaneus avulsion fracture were treated operatively in diabetic patients, and reported.

• The Journal of Korean Physical Therapy
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• v.18 no.2
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• pp.17-24
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• 2006

Purpose: This study was aimed for service to clinical data of physical therapy necessity of bone complication through analysis method of BMD (bone mineral density) used DEXA (dual energy X-ray absorptiometry) to their skeletal system for physical therapy assesement and intervention program in type II diabetic patients. Methods: Experimental group of 75 subjects and comparison group of 62 subjects were participated in type II diabetic patients(40-80 ages). BMD was measured by DEXA. BMD change of BMI score and BMD comparison of age and sex would be known. Results: This study was found that decreased BMD and increased osteopenea in type II diabetes. In particular, women were lower BMD and higher incidence of osteopenea than men. Men showed significant difference in normal group. Influence of type II diabetes was great on change of BMD in men. however, it showed no significant difference from normal group. Conclusion: it was found that skeletal system complication by type II diabetes had some relations. Because reduction of BMD had a great danger to induce trauma by fall or degenerative disease of system, evaluation of proper physical therapy for its prevention and improvement and intervention program are needed. In addition, it would be important to divide type II diabetic patients into osteopenea and osteoporosis changes of skeletal system at comprehensive aspect of physical therapy.

• Journal of Korean Foot and Ankle Society
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• v.19 no.2
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• pp.73-76
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• 2015

The calcaneal insufficiency avulsion fracture usually occurs in an area of fused apophysis in adults without significant history of trauma or overuse activities. It is an uncommon injury which has been described in patients with complicated diabetes, Charcot neuroarthropathy, amyloidosis with neuropathy, severe osteoporosis, and other conditions. Discussion of the issue of fracture location is still not sufficient. We report on a case of a 50-year-old male who experienced a non-traumatic diabetic calcaneal insufficiency fracture. Intraoperatively, a biopsy specimen was obtained from the exposed fracture site for histological study. We assume that the calcaneal fused apophyseal line is the weak point of failure due to various incomplete mixtures of trabecular bone, woven bone, and cartilaginous tissues, and may fail when repeated tensile stress is imposed.

• Journal of Korean Foot and Ankle Society
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• v.12 no.2
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• pp.230-233
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• 2008

The avulsion fracture of the calcaneal tuberosity is rare injury. Usually, it occurs from indirect trauma in old patients with osteoporosis or in patients with diabetic neuropathy. Especially, the bone and joint damage occurred in active patient with severe sensory loss or arthropathy related to nerve damage regardless of the cause is referred to neuropathic arthropathy. Generally, a patient with nondisplacement or minimally displacement is treated by conservative therapy and a patient with severe displacement is treated by open reduction and internal fixation. We experienced a 33 years-old woman with diabetes mellitus who had the displaced avulsion fracture of the calcaneal tuberosity without significant trauma and did not treat. We report upon this case at the 2 years follow-up.