• Journal of mucopolysaccharidosis and rare diseases
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• 제5권1호
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• pp.1-7
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• 2021

Gaucher disease (GD, OMIM #230800 OMIM#230800) is a rare, autosomal recessive inherited metabolic disorder caused by mutation in GBA1 encoding the lysosomal enzyme, glucocerebrosidase. The deficiency of glucocerebrosidase leads to an accumulation of its substrate, glucosylceramide in macrophages of various tissues. Common clinical manifestations include cytopenia, splenomegaly, hepatomegaly, and bone lesions. The phenotype of GD is classified into three clinical categories: Type 1 (non-neuronopathic) is characterized by involvements on the viscera, whereas types 2 and 3 (neuronopathic) are associated with not only visceral symptoms but also neurological impairment, either severe in type 2 or variable in type 3. A diagnosis of GD can be confirmed by demonstrating the deficiency of acid glucocerebrosidase activity in leukocytes. Mutations in the GBA1 should be identified as they may be of prognostic value in some cases. Biomarkers including Chitotriosidase, CCL18, and glucosylsphingosine (lyso-GL1) are useful in diagnosis and treatment monitoring. Currently available disease-specific treatment in Korea consists of intravenous enzyme replacement therapy and substrate reduction therapy. For enhancing long-term prognosis, the onset of Parkinson's disease and Lewy body dementia, or the occurrence of a blood disease or cancer (hepatocellular carcinoma) should be monitored in older patients. The development of new strategies that can modify the neurological phenotype are expected, especially in Asia including Korea, where the prevalence of neuronopathic GD is relatively higher than that in western countries.

• Journal of Genetic Medicine
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• 제19권2호
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• pp.63-75
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• 2022

Purpose: Osteoporosis is a common calcium and metabolic skeletal disease which is characterized by decreased bone mass, microarchitectural deterioration of bone tissue and impaired bone strength, thereby leading to enhanced risk of bone fragility. In this study, we aimed to identify novel genes for susceptibility to osteoporosis and/or bone density. Materials and Methods: To identify differentially expressed genes (DEGs) between control and osteoporosis-induced cells, annealing control primer-based differential display reverse-transcription polymerase chain reaction (RT-PCR) was carried out in pre-osteoblast MC3T3-E1 cells. Expression levels of the identified DEGs were evaluated by quantitative RT-PCR. Association studies for the quantitative bone density analysis and osteoporosis case-control analysis of single nucleotide polymorphism (SNPs) were performed in Korean women (3,570 subjects) from the Korean Association REsource (KARE) study cohort. Results: Comparison analysis of expression levels of the identified DEGs by quantitative RT-PCR found seven genes, Anxa6, Col5a1, Col6a2, Eno1, Myof, Nfib, and Scara5, that showed significantly different expression between the dexamethason-treated and untreated MC3T3-E1 cells and between the ovariectomized osteoporosis-induced mice and sham mice. Association studies revealed that there was a significant association between the SNPs in the five genes, ANXA6, COL5A1, ENO1, MYOF, and SCARA5, and bone density and/or osteoporosis. Conclusion: Using a whole-genome comparative expression analysis, gene expression evaluation analysis, and association analysis, we found five genes that were significantly associated with bone density and/or osteoporosis. Notably, the association P-values of the SNPs in the ANXA6 and COL5A1 genes were below the Bonferroni-corrected significance level.

• International Journal of Oral Biology
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• 제42권4호
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• pp.163-168
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• 2017

Osteoporosis is a metabolic bone disease that is characterized by low bone mass resulting from an increase in bone resorption relative to bone formation. The most current therapies for osteoporosis have focused on inhibiting bone resorption by osteoclasts. The purpose of this study is to develop new anabolic agents for treatment of osteoporosis that have fewer risks compared to conventional therapies. We searched the natural products that were derived from the traditional Asian medicines which have been used for treatment of bone related diseases. Icaritin is a flavonoid glycoside derived from the herb Epimedium which has beneficial effects on bone formation. To determine the effect of icaritin on bone formation, we examined the effect of icaritin on MC3T3-E1 cell proliferation and differentiation. For determining the effects of icaritin on proliferation, we performed the MTT assay using MC3T3-E1 cells. To evaluate whether icaritin could promote the osteogenic differentiation of MC3T3-E1 cells, alkaline phosphatase (ALP) activity and mRNA expressions of Runx2, osteocalcin (OCN), RANKL, and osteoprotegerin (OPG) were determined. Icaritin increased MC3T3-E1 cell proliferation. Icaritin increased the ALP activity of MC3T3-E1 cells on 72 hour culture in osteogenic media. mRNA expression of Runx2 was increased after 24 hour culture with icaritin. mRNA expression of osteocalcin was increased after 72 hour culture with icaritin. In addition, icaritin increased the mRNA expressions of OPG and RANKL. However, icaritin increased the mRNA expression of OPG much more than that of RANKL, and then, it increased the OPG/RANKL ratio. These results suggest that icaritin promotes osteogenic differentiation of osteoblasts and decreases osteoclast formation regulated by osteoblasts.

• 대한치과보철학회지
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• 제30권4호
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• pp.526-540
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• 1992

Osteoporosis, a well known metabolic bone disease, occurs due to imbalance of bone formings and resorptions. In an attempt investigate if postmenopausal osteoporosis would have influence on the mandible, histomorphometric analysis was performed in the mandible and the femur of the albino rats. Osteoporosis was induced by bilateral oophorectomy. To determine the effect of calcitonin, calcitonin(Asahi Chemical Co., Japan) was injected in the oophorectomized rats. The results were as follows : 1. The width of cortical bone of the femur was decreased in the oophorectomized group compared to the normal control and calcitonin injected groups and the porosity of cortical bone of the femur was increased in the oophorectomized group compared to the normal control and calcitonin injected groups. 2. The osteoid tissue and resorption lacuna of the femur was increased in both oophorectormized and calcitonin injected groups than the normal control group. 3. The width of cortical bone of the mandible was decreased in the oophorectomized group compared to the normal control and calcitonin injected groups. 4. The porosity of cortical bone of the mandible was decreased in both oophorectomized and calcitonin injected groups than the normal control group. 5. The relative volume of trabecular bone of the mandible was decreased in the oophorectomized group compared to the normal control and calcitonin injected groups. 6. The osteoid tissue of the mandible was increased in the calcitonin injected group than the normal control and oophorectomized groups. 7. The resorption lacuna of the mandible was increased in both oophorectomized and calcitonin injected groups, particularly in the oophorectomized group.

• Journal of Acupuncture Research
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• 제26권2호
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• pp.91-101
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• 2009

Objectives: Osteoporosis is the most common metabolic disease of the bone, and is one of the most important major public health problems world wide. It is more occurred in female than male, but as the osteoporosis of men is increasing, therefore bone fractures of men are increasing. So we investigated the factors which are related to Bone Mineral Density(BMD) of male for prevention of osteoporosis. Methods: We measured the Bone Mineral Density(BMD) of lumbar spine($L_2$-$L_4$) and femoral neck in 5198 male, using dual energy X-ray absorptionmetry(DEXA; DPX-alpha). And then we analysed the 8 factors - age group, bone mass index(BMI), amount of smoking, drinking, exercise, and fast blood sugar, gastric disease, thyroid disease - which are related to BMD of male. Results: 1. In age group according to ${\ll}$Hwangjaenaekyong Somun, 黃帝內徑 素問${\gg}$, T-score was the highest at 17-24(三八歲) years group and decreased rapidly after 57-64(八八歲) years group in both lumbar spine($L_2$-$L_4$) and femoral neck. Therefore we concluded that T-score of male in lumbar spine($L_2$-$L_4$) and femoral neck change according to age group in ${\ll}$Hwangjaenaekyong Somun, 黃帝內徑 素問${\gg}$. 2. In BMI(body mass index), T-score of lumbar spine($L_2$-$L_4$) and femoral neck were the highest in obese group than non-obese group. In comparison of age group according to BMI, T-score of lumbar spine($L_2$-$L_4$) was significant difference in 17-72 years group and T-score of femoral neck was in 25-72 years group. 3. In exercise, T-score of lumbar spine($L_2$-$L_4$) and femoral neck was increasing as exercising more. In comparison of age group according to exercise, Both T -score of lumbar spine and femoral neck were significant difference in 25-72 years old. 4. T-score of lumbar spine($L_2$-$L_4$) was the highest in men who have taken exercise daily, and T-score of femoral neck was the highest in men who have taken exercise 1-3 times for a week. Conclusions : The age group in ${\ll}$Hwangjaenaekyong Somun, 黃帝內徑 素問${\gg}$ is related to BMD of men. And risk factors - BMI, exercise - are related to BMD of men. Therefore we expect that this study will help for prevention of osteoporosis of men.

• 한국식품영양과학회지
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• 제38권12호
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• pp.1815-1819
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• 2009

여러 단백질과 다양한 무기질(칼슘 등)을 함유한 단단한 기관인 골은 정상적으로 다른 연조직 세포로 무기질을 공급하는 역할을 수행하지만, 비타민 결핍, 노화, 폐경기 및 대사성 질환 등으로 인해서 골다공증이 유발되고 동시에 다양한 연조직(심장, 대동맥, 신장, 허파, 췌장 등)의 석회화가 빈번히 유도된다. 같은 중간엽 줄기세포로부터 유래되는 연조직을 구성하는 세포와 조골세포 사이에서는 상호 횡간의 분화가 될 수 있는 여지가 있어, 연조직 세포는 칼슘 축적으로 골을 형성하는 조골세포와 유사한 세포로 분화될 수 있다. 연조직을 이루는 다양한 연조직 장기의 칼슘 축적으로 인한 석회화는 치명적인 장기손상으로 생명을 위협할 수 있으므로 적극적인 예방과 치료가 중요할 것이다. 골다공증과 연조직 석회화는 상호 밀접한 연계성이 있어 한 가지의 질병이 진행되면 다른 질병이 연속적으로 발병할 우려가 있으므로 초기 질병에 대한 적극적인 치료가 필요하다. 향후 초고속고령화 사회 진입으로 이의 두 질환의 급격한 증가가 예상되므로, vitamin K와 D를 비롯한 다양한 무기질을 균형적으로 조절할 수 있는 식습관과 다량의 항산화제를 함유한 음식물 섭취로 이의 질환을 예방할 수 있을 것이다.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• 제35권5호
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• pp.353-360
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• 2009

Bisphosphonates are compounds widely used in the treatment of various metabolic and malignant bone disease. Recently, an association between bisphosphonate use and a rare dental condition termed 'osteonecrosis of the jaw(ONJ)' has been reported. Bisphosphonate-related osteonecrosis of the jaw(BRONJ) is rare, but serious, side effect of bisphosphonate therapy in affected patients. It is characterized by poor wound healing and spontaneous intra-oral soft tissue break down, which lead to exposure of necrotic maxillary and mandibular bone. We reviewed 11 patients of BRONJ visited Ajou University Hospital Dental clinic from May 2007 to November 2008. The management of the patients included cessation of bisphosphonate therapy and various surgical restorative procedures and conservative care there after. Aggressive debridement is contraindicated. A new complication of bisphosphonate therapy administration, osteonecrosis of jaws, seems to be developing. The improved results after cessation of the medication should make clinicians reconsider the merits of the rampant use of bisphosphonates, while further investigation is needed to completely elucidate this complication.

• Molecules and Cells
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• 제25권3호
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• pp.352-357
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• 2008

Osteoprotegerin (OPG) is a soluble decoy receptor that inhibits osteoclastogenesis and is closely associated with bone resorption processes. We have designed and determined the solution structures of potent OPG analogue peptides, derived from sequences of the cysteine-rich domain of OPG. The inhibitory effects of the peptides on osteoclastogenesis are dose-dependent ($10^{-6}M-10^{-4}M$), and the activity of the linear peptide at $10^{-4}M$ is ten-fold higher than that of the cyclic OPG peptide. Both linear and cyclic peptides have a ${\beta}$-turn-like conformation and the cyclic peptide has a rigid conformation, suggesting that structural flexibility is an important factor for receptor binding. Based on structural and biochemical information about RANKL and the OPG peptides, we suggest that complex formation between the peptide and RANKL is mediated by both hydrophobic and hydrogen bonding interactions. These results provide structural insights that should aid in the design of peptidyl-mimetic inhibitors for treating metabolic bone diseases caused by abnormal osteoclast recruitment.

• 한국방사선학회논문지
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• 제11권1호
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• pp.43-48
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• 2017

최근 동위원소를 이용한 뼈 스캔 (Bone Scan)검사 후 골밀도 (BMD; Bone Mineral Density)검사를 당일검사로 병행한 경우 이로 인한 골밀도 측정값에 오차 발생 가능성이 제기되고 있으나 방사성의약품 표지화합물 투여 후 이중에너지 X선을 이용한 골밀도 측정값 변화에 대한 임상적 자료가 미비하여 핵의학 체내검사 후 당일 골다공증 검사의 측정값에 대한 논란의 소지가 있다. 따라서 동위원소 표지화합물인 $^{99m}Tc-MDP$가 골밀도 측정값에 영향을 미치는지 임상적 측면에서 실험하였다. 실험에 참가한 대상자의 평균 나이는 $35.17{\pm}9.45$세로 실험 대상자 17명 중 대사성 질환과 골밀도 측정에 영향을 줄 수 있는 허리뼈 압박골절 및 몸쪽 넓적다리뼈 골절이 있는 자를 제외한 12명 중 정상 골밀도 T-scores>-1.0의 환자 6명을 대상으로 $^{99m}Tc-MDP$ 투여 전 후 측정값을 분석한 결과 허리뼈에서 전 후 각각 평균 $0.975{\pm}0.084g/cm^2$, $0.966{\pm}0.078g/cm^2$으로 $0.009g/cm^2$ 증가, 우측 몸쪽 넓적다리뼈에서는 전 후 각각 평균 $0.909{\pm}0.078g/cm^2$, $0.913{\pm}0.086g/cm^2$으로 $0.004g/cm^2$ 감소, 좌측 몸쪽 넓적다리뼈에서는 각각 평균 $0.887{\pm}0.099g/cm^2$, $0.881{\pm}0.103g/cm^2$으로 $0.007g/cm^2$의 증가를 보여 몸쪽 넓적다리뼈 보다 허리뼈에서 더 큰 골밀도 변화를 보여주었다. 그러나 허리뼈와 몸쪽 넓적다리뼈 전체에서 전 후 변화 평균은 $0.0038{\pm}0.014g/cm^2$으로 골밀도 측정값에 유의한 영향이 없음을 알 수 있으며, 또한 두 실험간 전체 상관계수는 0.987으로 방사성동위원소 표지화합물인 $^{99m}Tc-MDP$ 투여가 골밀도 측정값에 영향을 주지 않았다. 따라서 140 keV의 감마선 에너지를 방출하는 테크네슘 표지화합물을 이용한 뼈 스캔검사 후 골밀도 측정값에 유의한 영향을 미치지 않음을 확인하였다. 그러나 핵의학적 체내검사와 골다공증 검사를 당일로 검사함으로 인한 환자의 피폭을 고려한다면 시간 간격을 두고 검사를 시행하는 것이 좋을 것으로 사료된다.

• Molecules and Cells
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• 제23권2호
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• pp.246-251
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• 2007

Osteoporosis is a common metabolic bone disease characterized by low bone mineral density (BMD) with an increased risk of fracture. Low bone mass results from an imbalance between bone formation by osteoblasts and bone resorption by osteoclasts. Microphthalmia-associated transcription factor (MITF) plays a critical role in osteoclast development and thus is an important candidate gene affecting bone turnover and BMD. In order to investigate the genetic effects of MITF variations on osteoporosis, we directly sequenced the MITF gene in 24 Koreans, and identified fifteen sequence variants. Two polymorphisms (+227719C > T and +228953A > G) were selected based on their allele frequencies, and then genotyped in a larger number of postmenopausal women (n = 560). Areal BMD ($g/cm^2$) of the anterior-posterior lumbar spine and the non-dominant proximal femur was measured by dual-energy X-ray absorptiometry. We found that the MITF + 227719C > T polymorphism was significantly associated with low BMD of the trochanter (p = 0.005-0.006) and total femur (p = 0.02-0.03) (codominant and dominant models), while there was no association with BMD of the lumbar spine. The MITF+228953A > G polymorphism was also associated with low BMD of the femoral shaft (p = 0.05) in the recessive model. Haplotype analysis showed that haplotype 3 of the MITF gene (MITF-ht3) was associated with low BMD of the trochanter (p = 0.03-0.05) and total femur (p = 0.05) (dominant and codominant models). Our results suggest that MITF variants may play a role in the decreased BMD of the proximal femur in postmenopausal women.