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6 "Osteoprotegerin"
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Calcium & Bone Metabolism
Changes in Serum Dickkopf-1, RANK Ligand, Osteoprotegerin, and Bone Mineral Density after Allogeneic Hematopoietic Stem Cell Transplantation Treatment
Eunhee Jang, Jeonghoon Ha, Ki-Hyun Baek, Moo Il Kang
Endocrinol Metab. 2021;36(6):1211-1218.   Published online December 8, 2021
DOI: https://doi.org/10.3803/EnM.2021.1248
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  • 103 Download
  • 1 Web of Science
  • 2 Crossref
AbstractAbstract PDFPubReader   ePub   
Background
Dickkopf-1 (DKK1) regulates bone formation by inhibiting canonical Wnt/β-catenin pathway signaling, and indirectly enhances osteoclastic activity by altering the expression ratio of receptor activator of nuclear factor-κB ligand (RANKL) relative to osteoprotegerin (OPG). However, it is difficult to explain continued bone loss after allogeneic stem cell transplantation (allo-SCT) in terms of changes in only RANKL and OPG. Few studies have evaluated changes in DKK1 after allo-SCT.
Methods
We prospectively enrolled 36 patients with hematologic malignancies who were scheduled for allo-SCT treatment. Serum DKK1, OPG, and RANKL levels were measured before (baseline), and at 1, 4, 12, 24, and 48 weeks after allo-SCT treatment. Bone mineral density (BMD) was assessed using dual-energy X-ray absorptiometry before (baseline) and 24 and 48 weeks after allo-SCT treatment.
Results
After allo-SCT treatment, the DKK1 level decreased rapidly, returned to baseline during the first 4 weeks, and remained elevated for 48 weeks (P<0.0001 for changes observed over time). The serum RANKL/OPG ratio peaked at 4 weeks and then declined (P<0.001 for changes observed over time). BMD decreased relative to the baseline at all timepoints during the study period, and the lumbar spine in female patients had the largest decline (–11.3%±1.6% relative to the baseline at 48 weeks, P<0.05).
Conclusion
Serum DKK1 levels rapidly decreased at 1 week and then continued to increase for 48 weeks; bone mass decreased for 48 weeks following engraftment in patients treated with allo-SCT, suggesting that DKK1-mediated inhibition of osteoblast differentiation plays a role in bone loss in patients undergoing allo-SCT.

Citations

Citations to this article as recorded by  
  • Fracture risk and assessment in adults with cancer
    Carrie Ye, William D. Leslie
    Osteoporosis International.2023; 34(3): 449.     CrossRef
  • Short-Term Impact of Hematopoietic Stem Cell Transplantation in Leukemia Patients on Bone Bio Markers, Electrolytes and Blood Profile
    Rhythm Joshi, Zehva Khan, Aakriti Garg, Dinesh Bhurani, Nidhi B Agarwal, Ubada Aqeel, Mohd Ashif Khan
    OBM Transplantation.2023; 07(02): 1.     CrossRef
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The Effects of Osteoprotegerin Polymorphism on Bone Mineral Metabolism in Korean Women with Perimenopause.
Ki Won Oh, Eun Joo Yun, Eun Jung Rhee, Won Young Lee, Ki Hyun Baek, Moo Il Kang, Cheol Young Park, Sung Hee Ihm, Moon Gi Choi, Hyung Joon Yoo, Sung Woo Park
J Korean Endocr Soc. 2005;20(3):204-215.   Published online June 1, 2005
DOI: https://doi.org/10.3803/jkes.2005.20.3.204
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AbstractAbstract PDF
BACKGROUND
Osteoprotegerin(OPG) is a recently identified cytokine, which acts as a decoy receptor for the receptor activator of the NF-kappaB ligand(RANKL), and has also been shown to be an important inhibitor of osteoclastogenesis in animal models. However, the relationship between OPG gene polymorphism and female bone stati in human populations is unclear. In this study, the relationship between OPG gene polymorphisms and bone mineral metabolism in healthy Korean women was investigated. METHODS: We observed 251 healthy women(mean age, 51.3+/-6.9 yr). The serum OPG concentrations were determined using ELISA, and the biochemical markers of bone turnover and FSH measured using standard methods. The bone mineral densities at the lumbar spine and femoral neck were measured by dual energy x-ray absorptiometry. The A163G, G209A, T245G and T950C polymorphisms of the OPG gene were analyzed by allelic discrimination using the 5 nuclease polymerase chain reaction assay. RESULTS: The lumbar spine BMD of premenopausal women was marginally decreased in the variant allele group compared to the wild type group(A163G, 0.98+/-0.14g/cm2[GG+GA] vs. 1.05+/- 0.15g/cm2[AA], P =0.070; T245G, 0.97+/-0.13g/cm2[GG+GT] vs. 1.04+/-0.15g/cm2[TT], P=0.056). In the linkage of polymorphisms A163G and T245G, the lumbar spine BMD of premenopausal women was marginally decreased in the variant allele group compared to the wild type group([AATT] vs. [AGTG+AGGG+GGTG+GGGG]: 1.04+/-0.15 vs. 0.97+/- 0.13; P=0.072). However, there were no differences in the serum OPG levels and bone turnover markers among the different genotypes. CONCLUSION: The A163G and T245G polymorphisms of the OPG gene were observed to be marginally associated with the lumbar spine BMD in healthy premenopausal Korean women, but further studies will be needed to clarify this relationship
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Relationship between Circulating Osteoprotegerin and Cardiovascular Risk Factors in Women.
Ki Won Oh, Eun Joo Yun, Eun Sook Oh, Eun Jung Rhee, Won Young Lee, Ki Hyun Baek, Kun Ho Yoon, Moo Il Kang, Cheol Young Park, Moon Ki Choi, Hyung Joon Yoo, Sung Woo Park
J Korean Endocr Soc. 2005;20(1):52-63.   Published online February 1, 2005
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AbstractAbstract PDF
BACKGROUND
Osteoprotegerin(OPG) is a recently identified cytokine, which acts as a decoy receptor for the receptor activator of NF-B ligand(RANKL). OPG has been shown to be an important inhibitor of osteoclastogenesis and arterial calcification in animal models. Recently, OPG has been proposed as a link molecule between osteoporosis and arterial calcification. However, the relationship between circulating OPG levels and cardiovascular disease in human populations is unclear. Thus, the aim of this study was to investigate the relationship between circulating OPG levels and cardiovascular risk factors in women. METHODS: The subjects were 286 women, with a mean age of 51.5 yr. The blood pressure, body mass index(BMI) and waist to hip ratio(WHR) were examined and the serum concentrations of OPG determined by ELISA. The fasting glucose levels, serum lipid profiles and follicle stimulating hormone (FSH) were measured by standard methods. RESULTS: A significant association was observed between the serum OPG levels, age and WHR(r=0.134, P<0.05). Also, the serum OPG levels were significantly correlated with the serum total cholesterol and low density lipoprotein cholesterol levels(r=0.175, P<0.01; r=0.176, P<0.01). Conversely, there was a nonsignificant relationship between the serum OPG levels, blood pressure and fasting glucose levels. The mean serum OPG levels were found to be about 11% greater in post-than premenopausal women(mean+/-SD, 1358.5+/-380.0 vs. 1228.8+/-407.7pg/mL, respectively(P<0.001). There was a significant association between the serum OPG and serum FSH levels(r=0.176, P<0.01). CONCLUSION: In conclusion, our data show that the levels of circulating OPG are partially associated with the cardiovascular risk factors and female hormonal status in healthy women. These data suggest that OPG may be an important paracrine factor of cardiovascular disease in human female populations.
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Relationship between Serum Osteoprotegerin-Receptor Activator of NF-kappaB Ligand Levels and Bone Mineral Metabolism in Men.
Ki Won Oh, Eun Joo Yun, Eun Jung Rhee, Won Young Lee, Ki Hyun Baek, Moo Il Kang, Cheol Young Park, Sung Hee Ihm, Moon Gi Choi, Hyung Joon Yoo, Sung Woo Park
J Korean Endocr Soc. 2004;19(4):332-345.   Published online August 1, 2004
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AbstractAbstract PDF
BACKGROUND
Osteoporosis is a growing health problem, not only in women, but in men also. Sex hormones and insulin-like growth factor-I (IGF-I) have been shown to be the major determinant in male bone metabolism. Osteoprotegerin (OPG) is a recently identified cytokine, which acts as a decoy receptor for the receptor activator of the NF- B ligand (RANKL). OPG and RANKL have been shown to be important regulators of osteoclastogenesis in animal models. The relationship between the OPG-RANKL system and male bone status in human populations is unclear. The aim of this study was to investigate the relationship between circulating the OPG-RANKL system and bone mineral metabolism in 80 Korean men. METHODS: The subjects of this study were 80 men aged between 42 and 70 (mean age, 54.5 yr). The serum concentrations of OPG and RANKL were measured by ELISA. The serum concentrations of estradiol, total testosterone, IGF-I and biochemical markers of bone turnover were measured by standard methods. The bone mineral densites (BMD) at the lumbar spine and femoral neck were measured by dual energy x-ray absorptiometry. RESULTS: A significant correlation was observed between the serum OPG/RANKL ratios and osteocalcin levels (r=-0.229, p<0.05). The serum OPG levels were significantly correlated to the femoral neck BMD (r=-0.227, p<0.05). The mean value of the serum OPG was found to be greater in patients with osteoporosis at the femoral neck (mean SD, 4.72.1 pmol/L) than in subjects with a normal BMD (3.30.9 pmol/L, p<0.05). The serum RANKL/OPG ratios were significantly positively correlated to the serum estradiol level (r=0.401, p<0.001). Also, there was a significant negative correlation between the serum OPG and estradiol levels (r=-0.288, p<0.05). In a multiple regression analysis, the BMI, serum OPG and RANKL levels, and the serum IGF-I level were identified as significant predictors of the femoral neck BMD. In another multiple regression analysis, only the serum estradiol level was identified as a significant predictor of the serum OPG level. CONCLUSION: In conclusion, our data show that the serum OPG and RANKL levels are partly associated with bone mineral metabolism, and are related to the endogenous estrogen levels in human male populations. Therefore, the possibility exists that the OPG-RANKL system may be a mediator of the estradiol in male bone metabolism. However, there have been few study published on the relation between the serum OPG and estradiol levels in men. Further studies are needed to clarify this relationship
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The Effects of C161-->T Polymorphisms in Exon 6 of Peroxisome Proliferator-Activated Receptor- Gene on Bone Mineral Metabolism and Serum Osteoprotegerin Levels in Healthy Korean Middle-aged Men.
Eun Jung Rhee, Won Young Lee, Se Yeon Kim, Eun Sook Oh, Ki Hyun Baek, Ki Won Oh, Kyung Chang Park, Ki Ok Han, Hyun Koo Yoon, Moo Il Kang, Sun Woo Kim
J Korean Endocr Soc. 2004;19(2):181-193.   Published online April 1, 2004
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AbstractAbstract PDF
BACKGROUND
The peroxisome proliferator-activated receptor (PPAR) is a member of the nuclear receptor family known to be involved in adipocyte differentiation. Recent studies have revealed the inhibitory role of PPAR in osteoblastogenesis, which suggests its possibility as a candidate gene for osteoporosis. The frequency of C161-->T substitution in exon 6 of PPAR was observed in Korean men and the association of different genotypes with bone turnover markers, bone mineral density (BMD) and serum osteoprotegerin (OPG), which play inhibitory roles in osteoclastogenesis, examined. METHODS: In 72 healthy Korean men (mean age 54.5 6.4 yrs; range 42~69 yrs), anthropometric measurements, and lumbar spine and femoral neck BMD, and bone turnover markers, such as alkaline phosphatase (ALP), serum calcium, phosphorus, osteocalcin and cross-linked C-telopeptides of type I collagen (ICTP) measurements were performed. The levels of serum testosterone, estradiol and insulin-like growth factor (IGF-I), and those of serum OPG levels, were measured with a sandwich enzyme-linked immunosorbent assay (ELISA) method. The DNAs were extracted from the samples, and polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and the sequencing of the products were performed to confirm the substitution. RESULTS: The allele frequencies were 0.799 and 0.201 for the C and T allele, respectively, which were in Hardy-Weinberg equilibrium (p=0.80). Subjects with the CT genotype were older and those with the T allele showed higher blood pressure levels and lower body mass indices (p<0.05) than those with the CC genotypes. There were no differences in the bone turnover markers between the different genotypes (p>0.05). The levels of serum testosterone, estradiol, IGF-I and OPG were not different among the different genotype groups (p>0.05). The lumbar, femoral neck BMD (g/cm2) and T scores were significantly lower in subjects with T alleles, and those with CT genotypes showed the lowest BMD values (p<0.05). When the subjects were divided into 3 groups, i.e., normal, osteopenic and osteoporotic groups, according to the lumbar spine BMD, the group with the T allele had a significantly higher prevalence of osteopenia and smaller numbers with normal BMD than those with the CC genotype (p=0.032). CONCLUSION: The frequencies of the C161-->T substitution in exon 6 of the PPAR gene in Korean men were similar to those observed in other races, and those with the T alleles showed significantly lower BMD values. These data imply the PPAR gene might be a candidate gene for the pathogenesis of osteoporosis
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The Regulation of OPG/OCIF mRNA Epression by IL-1beta in Peripheral Blood Mononuclear Cells.
In Gul Moon, Ho Yeon Chung, Chang Sun Hwang, Young Soon Kang, Mi Sun Chung, Han Jin Oh, Kyu Hong Choi, Sun Woo Kim, Eui Hyun Kim, Youn Yee Kim, Chang Hoon Yim, Ki VOk Han, Hak Chul Jang, Hyun Koo Yoon, In Kwon Han
J Korean Endocr Soc. 2000;15(2):204-213.   Published online January 1, 2001
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AbstractAbstract PDF
BACKGROUND
Osteoprotegerin(OPG) is a soluble member of the tumor necrosis factor(TNF) receptor family and inhibits osteoclastogenesis by interrupting the cell-to-cell interaction between osteoblastic/stromal cells and osteoclast progenitors. OPG is expressed in many tissues including osteoblasts and may act on bone tissues in a paracrine and/or autocrine fashion. Futhermore, many cytokines and growth factors are known to influence the regulation of OPG expression in osteoblastic/stromal cells. The aims of the present study were to examine whether or not OPG was expressed in human peripheral blood mononuclear cells(PBMCs) and to investigate the effects of IL-1beta, which were known as potent osteotropic agents, on the regulation of OPG mRNA in PBMCs. METHODS: PBMCs were isolated by centrifugation over Ficoll-Hypaque density gradients from postmenopausal women and cultured in 6-well plates containing alpha-MEM supplemented with 5% FBS. The expression of OPG mRNA in PBMCs was observed by RT-PCR in adherent and nonadherent cells on culture plates. To observe the effect of OPG expression by IL-1beta, we measured the concentration of OPG mRNA by altering the concentration and incubation time of IL-1beta. The measurement of OPG mRNA was done by semi-quantitative PCR and indicated as OPG/GAPDH. RESULTS: OPG was expressed both in cells attached to the surface of culture plates and in non-adherent cells for the incubation of peripheral blood mononuclear cells. The effect of OPG mRNA by IL-1beta tend to increase in accordance with the length of incubation time and maximizes at 12 hours of incubation time and shows 1.2-3.5 times higher than the standard level at the concentration of 0.5ng/ml. However, the increased quantity in concentration varies according to individuals.] CONCLUSION: OPG mRNA is expressed in peripheral blood mononuclear cells and known to be increased by IL-1beta.
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