دورية أكاديمية
The Expression of PHOSPHO1, nSMase2 and TNAP is Coordinately Regulated by Continuous PTH Exposure in Mineralising Osteoblast Cultures
| العنوان: | The Expression of PHOSPHO1, nSMase2 and TNAP is Coordinately Regulated by Continuous PTH Exposure in Mineralising Osteoblast Cultures |
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| المؤلفون: | Houston, D A, Myers, K, MacRae, V E, Staines, K A, Farquharson, C |
| بيانات النشر: | BMC |
| سنة النشر: | 2016 |
| المجموعة: | Edinburgh Napier Repository (Napier University Edinburgh) |
| مصطلحات موضوعية: | Endocrinology, Diabetes and Metabolism, Orthopedics and Sports Medicine, 616 Diseases, QP Physiology, Biomedical Science Research Group, Health |
| الوصف: | Sustained exposure to high levels of parathyroid hormone (PTH), as observed in hyperparathyroidism, are catabolic to bone. The increase in the RANKL/OPG ratio in response to continuous PTH, resulting in increased osteoclastogenesis is well established. However, the effects of prolonged PTH exposure on key regulators of skeletal mineralisation has yet to be investigated. This study sought to examine the temporal expression of PHOSPHO1, TNAP and nSMase2 in mineralising osteoblast-like cell cultures and to investigate the effects of continuous PTH exposure on the expression of these genes in vitro. PHOSPHO1, nSMase2 and TNAP expression in cultured MC3T3-C14 cells significantly increased from day 0 to day 10. PTH induced a rapid downregulation of Phospho1 and Smpd3 gene expression in MC3T3-C14 cells and cultured hemi-calvariae. Alpl was differentially regulated by PTH, displaying upregulation in cultured MC3T3-C14 cells and downregulation in hemi-calvariae. The effects of PTH on Phospho1 expression were mimicked with the cAMP agonist forskolin, and blocked by the PKA inhibitor PKI (5-24), highlighting a role for the cAMP/PKA pathway in this regulation. The potent down-regulation of Phospho1 and Smpd3 in osteoblasts in response to continuous PTH may provide a novel explanation for the catabolic effects on the skeleton of such an exposure. Furthermore, our findings support the hypothesis that PHOSPHO1, nSMase2 and TNAP function cooperatively in the initiation of skeletal mineralisation. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | unknown |
| تدمد: | 0171-967X |
| العلاقة: | http://researchrepository.napier.ac.uk/Output/462340Test; https://napier-repository.worktribe.com/file/462340/1/The%20Expression%20of%20PHOSPHO1,%20nSMase2%20and%20TNAP%20is%20CoordinatelyTest. |
| DOI: | 10.1007/s00223-016-0176-9 |
| الإتاحة: | https://doi.org/10.1007/s00223-016-0176-9Test https://napier-repository.worktribe.com/file/462340/1/The%20Expression%20of%20PHOSPHO1,%20nSMase2%20and%20TNAP%20is%20CoordinatelyTest. http://researchrepository.napier.ac.uk/Output/462340Test |
| حقوق: | openAccess ; http://creativecommons.org/licenses/by/4.0Test/ |
| رقم الانضمام: | edsbas.6C3E9C07 |
| قاعدة البيانات: | BASE |
| تدمد: | 0171967X |
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| DOI: | 10.1007/s00223-016-0176-9 |