Zoledronic acid at subtoxic dose extends osteoblastic stage span of primary human osteoblasts
| العنوان: | Zoledronic acid at subtoxic dose extends osteoblastic stage span of primary human osteoblasts |
|---|---|
| المؤلفون: | Stefano Tetè, Umberto Di Tore, Marialucia Gallorini, Viviana di Giacomo, Chiara Di Nisio, Vincenzo Luca Zizzari, Marianna De Colli, Vincenzo Salini, Amelia Cataldi, Susi Zara |
| المساهمون: | Zara, Susi, DE COLLI, Marianna, DI GIACOMO, Viviana, Zizzari, VINCENZO LUCA, DI NISIO, Chiara, Di Tore, Umberto, Salini, Vincenzo, Gallorini, Marialucia, Tetã, Stefano, Cataldi, Amelia |
| المصدر: | Clinical Oral Investigations. 19:601-611 |
| بيانات النشر: | Springer Science and Business Media LLC, 2014. |
| سنة النشر: | 2014 |
| مصطلحات موضوعية: | Apoptosis, Zoledronic Acid, Bone Density, 80 and over, Inner mitochondrial membrane, Aged, 80 and over, Membrane Potential, Mitochondrial, Human osteoblast, Bone Density Conservation Agents, Diphosphonates, biology, Blotting, Chemistry, Osteoblast, Imidazoles, Cell Differentiation, Biological activity, Mitochondrial, Diphosphonate, Differentiation, Osteocalcin, Alkaline phosphatase, Western, Type I collagen, Human, medicine.medical_specialty, Bone Density Conservation Agent, Cell Survival, Blotting, Western, Enzyme-Linked Immunosorbent Assay, In Vitro Techniques, PGE2, Real-Time Polymerase Chain Reaction, Membrane Potential, Collagen Type I, Dinoprostone, Bone resorption, Andrology, medicine, Humans, Viability assay, Imidazole, General Dentistry, Zoledronic acid, Aged, Osteoblasts, Osteonecrosis of the jaw, In Vitro Technique, Interleukin-6, Apoptosi, Surgery, Dentistry (all), biology.protein |
| الوصف: | This study aimed to check the effect of zoledronic acid (ZA) at subtoxic dose on human osteoblasts (HOs) in terms of cell viability, apoptosis occurrence, and differentiation induction. ZA belongs to the family of bisphosphonates (BPs), largely used in the clinical practice for the treatment of bone diseases, often associated with jaw osteonecrosis onset. Their pharmacological action consists in the direct block of the osteoclast-mediated bone resorption along with indirect action on osteoblasts. HOs were treated choosing the highest limit concentration (10−5 M) which does not induce toxic effects. Live/dead staining, flow cytometry, mitochondrial membrane potential assay, osteocalcin western blotting, gp38 RT-PCR, collagen type I, PGE2, and IL-6 ELISA assays were performed. Similar viability level between control and ZA-treated samples is found along with no significant increase of apoptotic and necrotic cells in ZA-treated sample. To establish if an early apoptotic pathway was triggered, Bax expression and mitochondrial membrane potential were evaluated finding a higher protein expression in control sample and a good integrity of mitochondrial membrane in both experimental points. Type I collagen secretion and alkaline phosphatase (ALP) activity appear increased in ZA-treated sample, osteocalcin expression level is reduced in ZA-treated cells, whereas no modifications of gp38 mRNA level are evidenced. No statistical differences are identified in PGE2 secretion level whereas IL-6 secretion is lower in ZA-treated HOs with respect to control ones. These results highlight that ZA, delaying the osteoblastic differentiation process versus the osteocytic lineage, strengthens its pharmacological activity enhancing bone density. The knowledge of ZA effects on osteoblasts at subtoxic dose allows to improve therapeutic protocols in order to strengthen drug pharmacological activity through a combined action on both osteoclastic and osteoblastic cells. |
| تدمد: | 1436-3771 1432-6981 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::f9dffd4929e5cd32d7ce77117eacc2d2Test https://doi.org/10.1007/s00784-014-1280-8Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....f9dffd4929e5cd32d7ce77117eacc2d2 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14363771 14326981 |
|---|