• Title/Summary/Keyword: PTH

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Intermittent Administration of Parathyroid Hormone for Orthodontic Tooth Movement in Mongrel Dogs: Preliminary Study

  • Won-Ho Kim;Bo Ram Lee;Hey-Yun Kim;Minji Kim;Jin-Woo Kim
    • Journal of Korean Dental Science
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    • v.16 no.2
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    • pp.182-191
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    • 2023
  • Purpose: This study investigated the orthodontic tooth movement after weekly parathyroid hormone (PTH) injection in mongrel dogs and analyzes bone formation activity on the tension and pressure sides of the tooth movement in mongrel dogs. Materials and Methods: Three mongrel dogs were used in this study. The first premolar was extracted and orthodontic force using 150 g of closed coil springs between the canine and second premolar was applied. The low-dose PTH group (PTH_1) and high-dose PTH group (PTH_2) received weekly injections of 1.61 ㎍/kg and 3.23 ㎍/kg of PTH, respectively. The control group received weekly injections of 1 ml of saline. Clinical, histomorphometric analysis were carried out. Result: The orthodontic tooth movement was greatest in the PTH_2 group and the lowest in the control group. Fluorescence staining images showed higher bone remodeling on the tension side of the tooth movement in the PTH_1 and PTH_2 groups. PTH_2 group showed a thicker labeling band than the PTH_1 group. PTH_2 group showed the highest mineral apposition rate and bone formation rate, followed by the PTH_1 group and the control group. Conclusion: Weekly intermittent PTH injection, especially in the short-term and at higher doses with orthodontic force, successfully increased orthodontic tooth movement and bone remodeling in mongrel dogs.

Retrovirus Vector-Mediated Construction of Porcine Cell Lines Expressing Human PTH (Retrovirus Vector System을 이용한 hPTH가 발현되는 돼지 세포의 구축)

  • Jeong J. Y.;Koo B. C.;Kim N. H.;Kwon M. S.;Park S. H.;Kim T. O.
    • Reproductive and Developmental Biology
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    • v.28 no.3
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    • pp.197-202
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    • 2004
  • Human PTH (parathyroid hormone) is known to be efficacious for curing osteoporesis. In this study, we attempted to construct genetically modified porcine cell lines that can ultimately be used for donor cells in nuclear transfer-mediated transgenesis. By using retrovirus vectors carrying tetracycline-regulatory expression system and WPRE (woodchuck hepatitis virus posttranscriptional regulatory element) sequence, we could control PTH expression with tetracycline and boost the promoter activity. Considering that low or constitutive expression of the transgene has been one of major problems that needs to be solved in transgenic animal studies, our results could be helpful in successful production of transgenic pigs as bioreactors.

EFFECTS OF INTRACELLULAR SODIUM CONCENTRATION ON THE BONE RESORPTION IN ORGAN CULTURE (세포내 Sodium농도가 배양골조직 흡수에 미치는 영향에 관한 연구)

  • Lee, Tai-Joon;Yang, Won-Sik
    • The korean journal of orthodontics
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    • v.19 no.1 s.27
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    • pp.61-75
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    • 1989
  • Recently, indirect evidences suggest that Na-Ca exchange mechanism is involved in bone resorption. To study this suggestion, effects of several drugs which increase the intracellular sodium concentration by different mechanisms on the PTH-induced bone resorption were analysed employing organ culture. Ulnae and radii were removed from 19-day fetal rats, prelabelled by subcutaneous injection of $200{\mu}\;Ci^{45}CaC1_2$ on the 17th day of gestation, and then explanted on the membrane filters in organ culture dishes. For studying the effects of amiloride, ouabain, monensin, and veratridine on the PTH-induced bone resorption, control group was cultured in BGJb media containing PTH (0.4U/ml) while experimental group was cultured in BGJb media containing PTH and drugs. The effects of drugs on the PTH-induced bone resorption were observed by the ratios of $\%-release$ of $^{45}Ca$ between paired control and experimental groups. The results were as follows: 1. $^{45}Ca$ release was significantly increased by PTH (0.4U/ml) at 48 and 72 hours of culture. 2. Amiloride, at concentration of $500{\mu}M$, significantly inhibited the PTH-induced bone resorption after 48 and 72 hours of culture. 3. Ouabain, at concentration of 0.1 mM, presented significant inhibition of PTH-induced bone resorption after 48 and 72 hours of culture, and at 0.5mM and 1mM, presented significant inhibition of PTH-induced bone resorption after 72 hours of culture. 4. Monensin, at concentration of 500nM, significantly inhibited PTH-induced bone resorption after 72 hours of culture. 5. Veratridine, at concentration of 0.5mM, presented significant inhibition of PTH-induced bone resorption after 48 and 72 hours of culture, and at 1mM, presented significant inhibition of PTH-induced bone resorption after 72 hours of culture. Taken altogether, these results suggest that Na-Ca exchange mechanism play a role in PTH-induced bone resolution.

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The Negative Role of PDE4 on PTH-induced Signaling in Osteoblasts (조골세포내 PDE4에 의한 PTH 신호의 음성적 조절)

  • Park, Hyo-Jung;Noh, A-Long-Sae-Mi;Lee, Jung-Min;Yim, Mi-Jung
    • YAKHAK HOEJI
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    • v.54 no.5
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    • pp.410-415
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    • 2010
  • We explored the role of phosphodiesterase 4 (PDE4) on parathyroid (PTH)-induced signaling in osteoblasts. PTH was shown to increase the activity of PDE, mainly PDE4, in osteoblasts, which is partly attributable to elevated PDE4B and PDE4D mRNA expression. The use of PDE4 inhibitor strengthened the PTH-induced extracellular signal-regulated kinase (ERK) and p38 MAP kinase (MAPK) activation. Furthermore, the PDE4 inhibitor stimulated PTH-induced receptor activator of nuclear factor-${\kappa}B$ ligand (RANKL) expression in osteoblasts, which in turn increased osteoclast formation. Taken together, these data suggest the negative role of PDE4 on PTH-induced signaling in osteoblasts.

Efficacy and Safety of Cinacalcet for Secondary Hyperparathyroidism in Dialysis Patients and Drug Use Evaluation (투석환자의 이차성 부갑상선 기능 항진증 치료에서 cinacalcet의 유효성과 안전성 및 사용 적정성 평가)

  • Seo, Hee Nam
    • Korean Journal of Clinical Pharmacy
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    • v.23 no.2
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    • pp.142-150
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    • 2013
  • Background: Secondary hyperparathyroidism (SHPT) is common in patients with chronic kidney disease, affecting most of those who are receiving dialysis. Cinacalcet, a novel calcimimetic, targets the calcium-sensing receptor to lower PTH levels in dialysis patients. Objective: This study aimed to assess efficacy, safety and appropriateness of use of cinacalcet in dialysis patients. Method: This retrospective study was performed on total 24 cases with identified intact parathyroid hormone (iPTH), serum calcium and phosphorus levels before and 4 weeks after cinacalcet initiation at a teaching hospital from July 1st, 2011 to October 31st, 2012. Results: Cinacalcet decreased iPTH by 19% from baseline after 4weeks treatment and it was statistically significant (p<0.001). Cinacalcet also significantly decreased iPTH levels regardless of dialysis modality (hemodialysis group versus peritoneal dialysis group) and severity of SHPT (iPTH 300-800 pg/ml group versus iPTH >800 pg/ml group). Serum calcium, phosphorus and Ca x P levels were decreased without statistical significance. Gastrointestinal events, headache and hypocalcemia were the most common side effects. Monitoring for iPTH and serum calcium was not performed appropriately. 43.7% patients initiated cinacalcet therapy at serum calcium level< 9.0 mg/dl. Conclusion: In conclusion, cinacalcet lowers parathyroid hormone levels with no serious side effects. However, it is required to avoid cinacalcet treatment in patients with low serum calcium levels and monitor iPTH and serum calcium levels during cinacalcet administration.

Regulation of hPTH Expression In Virto Using the Tetracycline Inducible Retrovirus Vector System (Tetracycline Inducible Retrovirus Vector System을 이용한 In Vitro에서의 인간 부갑상선 호르몬의 발현 조절)

  • Koo, Bon-Chul;Kwon, Mo-Sun;Kim, Te-Oan
    • Reproductive and Developmental Biology
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    • v.30 no.3
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    • pp.157-162
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    • 2006
  • Endogenous 84 amino acid parathyroid hormone(PTH) is synthesized as a pre-pro hormone by the chief cells of the parathyroid glands. Physiological actions of PTH include regulation of bone metabolism, renal tubular reabsorption of calcium and phosphate, and intestinal calcium absorption. In addition, PTH stimulates new bone formation by extraordinary stimulation of osteoblastic activity and decreasing calcium excretion by the kidney. In this study, we constructed and tested retrovirus vectors designed to express the human parathyroid hormone(hPTH) gene under the control of the tetracycline-inducible promoters. To increase the hPTH gene expression at turn-on state, woodchuck hepatitis virus posttranscriptional regulatory element(WPRE) sequence was also introduced into retrovirus vector at downstream region of either the hPTH gene or the sequence encoding reverse tetracycline-controlled transactivator(rtTA). Transformed primary culture cells(porcine fetal fibroblast, PFF, chicken embryonic fibroblast, CEF) were cultured in the medium supplemented with or without doxycycline(tetracycline derivative) for 48 hours, and induction efficiency was measured by comparing the hPTH gene expression level using two step RT-PCR and ELISA Higher hPTH expression($3{\tims}10^4\;pg/ml,\;5.3{\times}10^4\;pg/ml$) and tighter expression control(up to 8 fold) were observed from the vector in which the WPRE sequence was placed at downstream of the hPTH gene. The resulting tetracycline inducible vector system may be helpful in solving serious physiological disturbance problems which have been a major obstacle in successful production of transgenic animals.

Retrovirus Vector System을 이용한 hPTH가 발현되는 돼지세포의 구축

  • 정지연;구본철;권모선;김태완;김남형
    • Proceedings of the KSAR Conference
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    • 2004.06a
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    • pp.211-211
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    • 2004
  • 골다공증 치료제로 이용되고 있는 hPTH (human parathyroid hormome)는 체내의 혈중 칼슘 농도를 조절하는 인간의 부갑상선 호르몬이다. 본 연구에서는 retrovirus vector system을 이용하여 hPTH를 효율적으로 생산하는 PFF (porcine fetal fibroblast) 돼지 세포를 구축하고자 하였다. hPTH 유전자는 갑상선 암 환자로부터 적출한 부갑상선 조직의 RNA를 주형으로 RT-PCR을 수행하여 cloning하였으며, 이 유전자가 RSV promoter 통제하에 발현되게끔 design된 retrovirus vector를 구축하였다. (중략)

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Effects of Dietary Ca Level and Hormones on Bone Density of Mouse (식이 Ca 수준과 호르몬 투여가 생쥐가 골밀도에 미치는 영향)

  • 정차권
    • Journal of Nutrition and Health
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    • v.29 no.9
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    • pp.943-949
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    • 1996
  • Bone mineral density depends largely on the status of dietary minerals such as Ca, P, Mg, and F and proteins, physical activities, parathyroid hormone(PTH), calcitonin(CT), and vitamin D. The decrease of bone density often results in bone fractures and osteoporosis which is prevalent among postmenopausal women. This study was intended to examine the role of parathyroid hormone, calcitonin and cholecaliferol in bone density of mice that were fed different dual photon energy beams. We have measured three major parts of the bone : whole body, head and femur. The results are summarized as follows : 1) Bone mineral density (BMD) was more increased by feeding high Ca diet compared to that of the low Ca diet. 2) Both PTH and Vit D3 enhanced BMD in all of the different Ca levels. 3) When the dietary Ca was deequate CT showed a synergistic effect with PTH in boosting bone density, while CT+Vit D3 showed a negative effect. 4) CT tended to inhibit the effect of increasing bone density by PTH and Vit D3 in medium and low Ca groups. 5) The effect of increasing bone density by PTH in the head of mouse increased when dietary Ca was lower : The increment of bone density by PTH in high, medium, and low Ca was 3%, 8%, 19%, respectively. 6) Femur bone density was affected significantly by dietary Ca levels than hormones. The above observations indicate that bone mineral density can be improved by high dietary Ca and hormone injections including PTH, CT and cholecalciferol, and thus proper dietary and hormonal treatment may be used in preventing bone fractures and osteoporosis.

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A Case of Pseudohypoparathyroidism in a Premature Infant (미숙아에서 발견된 가성부갑상선 기능저하증 1례)

  • Yang, Jong Il;Seo, Jang Won;Kim, Ji Young
    • Clinical and Experimental Pediatrics
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    • v.46 no.10
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    • pp.1032-1035
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    • 2003
  • In pseudohypoparathyroidism as reported by Albright in 1942, the parathyroid gland can normally synthesize and secrete parathyroid hormone(PTH). Pseudohypoparathyroidism has a similar biochemical finding with hypoparathyroidisms like hypocalcemia and hyperphosphatemia due to target tissue resistance to PTH. Administered PTH does not raise the serum levels of calcium and urinary phosphate. PTH activates G-protein in peripheral tissue and adenylate cyclase through a second messenger, cAMP. Pseudohypoparathyroidism produces hyperphosphatemia and hypocalcemia because of the resistance to PTH in peripheral tissue due to a defect of G-protein, although it releases PTH normally. According to the mechanism of resistance, pseudohypoparathyroidism is classified into types : Ia, Ib, Ic and psedopseudohypoparathyroism. Type Ia is accompanied by congenital growth retardation and abnormal bony development that shows mental retardation, obesity, low height, round face, short metacarpal bone and metatarsal bone, ectopic calcification, etc. We report a case of pseudohypoparathyroidism in a premature who shows hypocalcemia, hyperphosphatemia, elevation of serum PTH and 24 hr urinary basal c-AMP in biochemical tests without Albright's hereditary osteodystrophy at physical examination, accompanied by a spontaneous fracture in the femur.

Endoproteolytic Processing of Human Parathyroid Hormone in Saccharomyces cerevisiae Mutants Lacking Genes Encoding the Yap3, Mkc7, and Kex2 Endoproteases

  • Choi, Won-A.;Kang, Hyun-Ah;Chung, Bong-Hyun
    • Journal of Microbiology and Biotechnology
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    • v.9 no.5
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    • pp.679-682
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    • 1999
  • When the human parathyroid hormone (hPTH) is expressed as a secretory product in S. cerevisiae, most of the secreted hPTH is internally cleaved by endoproteolytic processing. To investigate whether the yeast endoproteases such as Kex2p, Yap3p, and Mkc7p are involved in the endoproteolytic processing of hPTH in S. cerevisiae, hPTH was expressed in S. cerevisiae mutants deficient in one or two of the following well-known endoproteases such as Kex2p, Mkc7p, and Yap3p. Among these mutants, the yap3-disrupted(yap3$\Delta$) and yap3/mkc7-disrupted (yap3Δmkc7$\Delta$) yeasts showed a significant reduction in the extent of hPTH proteolysis. In contrast, the mkc7-disrupted (mkc7$\Delta$) yeast did not reduce the proteolysis of hPTH as compared to the wild type. This suggests that Mkc7p is not involved in the endoproteolytic processing of hPTH. It was also found that the kex2-disrupted (kex2$\Delta$) mutant was not able to secrete a detectable amount of hPTH.

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