Potassium citrate prevents increased osteoclastogenesis resulting from acidic conditions: Implication for the treatment of postmenopausal bone loss
| العنوان: | Potassium citrate prevents increased osteoclastogenesis resulting from acidic conditions: Implication for the treatment of postmenopausal bone loss |
|---|---|
| المؤلفون: | Elena Torreggiani, Nicola Baldini, Donatella Granchi, Renata Caudarella, Annamaria Massa, Gemma Di Pompo |
| المساهمون: | Granchi, Donatella, Torreggiani, Elena, Massa, Annamaria, Caudarella, Renata, Di Pompo, Gemma, Baldini, Nicola |
| المصدر: | PLoS ONE PLoS ONE, Vol 12, Iss 7, p e0181230 (2017) |
| بيانات النشر: | Public Library of Science (PLoS), 2017. |
| سنة النشر: | 2017 |
| مصطلحات موضوعية: | 0301 basic medicine, Osteopenia and Osteoporosis, Drug Evaluation, Preclinical, lcsh:Medicine, Gene Expression, Osteoclasts, Pathology and Laboratory Medicine, Biochemistry, Mice, 0302 clinical medicine, Animal Cells, Osteogenesis, Potassium Citrate, Bone cell, Medicine and Health Sciences, lcsh:Science, RAW 264.7 Cell, Osteoporosis, Postmenopausal, Connective Tissue Cells, Multidisciplinary, Bone Density Conservation Agents, Alendronate, biology, Osteoblast, Osteogenesi, Cell Differentiation, Biological activity, Hydrogen-Ion Concentration, Enzymes, Connective Tissue, RANKL, Osteoclast, Alkaline phosphatase, Cellular Types, Anatomy, Acidosis, Research Article, Human, medicine.medical_specialty, Bone Density Conservation Agent, Phosphatase, chemistry.chemical_element, 030209 endocrinology & metabolism, Calcium, Osteocytes, NO, 03 medical and health sciences, Signs and Symptoms, Diagnostic Medicine, Internal medicine, Genetics, medicine, Animals, Humans, Bone, Cell Proliferation, Osteoblasts, Biochemistry, Genetics and Molecular Biology (all), Animal, lcsh:R, RANK Ligand, Phosphatases, Acid phosphatase, Biology and Life Sciences, Proteins, Cell Biology, Alkaline Phosphatase, medicine.disease, Culture Media, Osteopenia, Biological Tissue, RAW 264.7 Cells, 030104 developmental biology, Endocrinology, Agricultural and Biological Sciences (all), chemistry, Enzymology, biology.protein, Women's Health, lcsh:Q, Collagens, Developmental Biology |
| الوصف: | The extracellular acidic milieu in bones results in activation of osteoclasts (OC) and inhibition of osteoblasts (OB) causing a net loss of calcium from the skeleton and the deterioration of bone microarchitecture. Alkalinization through supplementation with potassium citrate (K citrate) has been proposed to limit the osteopenia progression, even though its pharmacological activity in bone microenvironment is not well defined. We evaluated if K citrate was able to prevent the adverse effects that acidic milieu induces on bone cells. OC and OB were maintained in neutral (pH 7.4) versus acidic (pH 6.9) culture medium, and treated with different K citrate concentrations. We evaluated the OC differentiation at seven days, by counting of multinucleated cells expressing tartrate-resistant acid phosphatase, and the activity of mature OC at 14 days, by quantifying of collagen degradation. To evaluate the effects on OB, we analyzed proliferation, mineralization, and expression of bone-related genes. We found that the low pH increased OC differentiation and activity and decreased OB function. The osteoclastogenesis was also promoted by RANKL concentrations ineffective at pH 7.4. Non-cytotoxic K citrate concentrations were not sufficient to steadily neutralize the acidic medium, but a) inhibited the osteoclastogenesis, the collagen degradation, and the expression of genes involved in RANKL-mediated OC differentiation, b) enhanced OB proliferation and alkaline phosphatase expression, whereas it did not affect the in vitro mineralization, and c) were effective also in OC cultures resistant to alendronate, i.e. the positive control of osteoclastogenesis inhibition. In conclusion, K citrate prevents the increase in OC activity induced by the acidic microenvironment, and the effect does not depend exclusively on its alkalizing capacity. These data provide the biological basis for the use of K citrate in preventing the osteopenia progression resulting from low-grade acidosis. |
| وصف الملف: | STAMPA |
| تدمد: | 1932-6203 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::30d149de199c3626f58e32164ec5c643Test https://doi.org/10.1371/journal.pone.0181230Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....30d149de199c3626f58e32164ec5c643 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 19326203 |
|---|