التفاصيل البيبلوغرافية
| العنوان: |
PROTEASOME INHIBITORS MODULATE OSTEOCYTE DEATH AND AUTOPHAGY IN MULTIPLE MYELOMA. |
| المؤلفون: |
Toscani, Denise, Ciullo, Alessandra, Bolzoni, Marina, Guasco, Daniela, Palma, Benedetta Dalla, Aversa, Franco, Giuliani, Nicola, PALUMBO, Carla, FERRETTI, Marzia |
| المساهمون: |
Toscani, Denise, Palumbo, Carla, Ciullo, Alessandra, Ferretti, Marzia, Bolzoni, Marina, Guasco, Daniela, Palma, Benedetta Dalla, Aversa, Franco, Giuliani, Nicola |
| سنة النشر: |
2014 |
| المجموعة: |
Archivio della ricerca dell'Università di Modena e Reggio Emilia (Unimore: IRIS) |
| مصطلحات موضوعية: |
Bone disease, Bortezomib, Myeloma |
| الوصف: |
Background: Cell death and autophagy are the main cellular processes involved in the regulation of bone remodeling by osteocytes. Recently we have demonstrated that an increased osteocyte death is involved in multiple myeloma (MM)-induced osteolysis through the upregulation of osteoclast recruitment. Aims: Because proteasome inhibitors including Bortezomib (BOR) are known to be able to target osteoblasts in this study we have investigated the potential effect of these drugs on osteocytes and their cell death and autophagy. Methods: Firstly the effect of the proteasome inhibitors BOR and MG262 on osteocyte viability was evaluated in vitro in murine osteocytic cell line MLO-Y4 and in the human pre-osteocytic one HOB-01. Both cell lines were co-coltured for 48 hours in the presence or absence of the human myeloma cell lines (HMCLs) RPMI8226 and JJN3, placed in a transwell insert in the presence or the absence of BOR or MG262. Moreover the effect of proteasome inhibitors on dexamethasone (DEX)-induced MLO-Y4 death, obtained at high doses (10-5-10-6M), was checked in combination with PTH(1-34). To evaluate the presence of autophagy and apoptosis in osteocytes, we checked the expression of both autophagic marker LC3 and apoptotic marker APAF-1 by confocal microscopy in the co-colture system with MLO-Y4 and RPMI-8226. Finally we performed a retrospective histological evaluation on bone biopsies of a cohort of 31 newly diagnosis MM underwent to different treatments including BOR-based regimen. Bone biopsies were obtained at the diagnosis and after an average time of 12 months of treatment. Osteocyte viability was evaluated in a total of 500 lacunae per histological sections. Results: The in vitro treatment with BOR or MG262 significantly blunted MLO-Y4 and HOB-01 cell death. Similarly, DEXinduced MLO-Y4 death was reduced by proteasome inhibitors. Interestingly, we found that both proteasome inhibitors potentiated the PTH (1-34) short-term effects on DEX-induced osteocyte death. Prevalence of autophagic cell death ... |
| نوع الوثيقة: |
article in journal/newspaper |
| اللغة: |
English |
| Relation: |
info:eu-repo/semantics/altIdentifier/wos/WOS:000342830901383; XIX Congress of the EUROPEAN HEMATOLOGY ASSOCIATION; volume:99; issue:suppl. 1; firstpage:352; lastpage:352; numberofpages:1; journal:HAEMATOLOGICA; http://hdl.handle.net/11380/1060600 |
| الاتاحة: |
http://hdl.handle.net/11380/1060600 |
| Rights: |
info:eu-repo/semantics/openAccess |
| رقم الانضمام: |
edsbas.1AF26A0A |
| قاعدة البيانات: |
BASE |