In vitro and in vivo evidences of osteocytes involvement in myeloma-induced osteoclast formation and bone disease

ABSTRACT: The involvement of osteocytes in multiple myeloma (MM)-induced osteoclast formation and the occurrence of bone lesions are still unknown. Osteocytes regulate bone remodeling at least in part through the cell death and apoptosis triggering osteoclast recruitment and formation. In this study, firstly we shown that MM cells increased osteocyte death and affect their transcriptional profile evaluated by microarray analysis up-regulating osteoclastogenic cytokines as interleukin (IL)-11. Consistently we show that the conditioned media of human pre-osteocytes co-cultured with MM cells significantly increased osteoclastogenesis. To translate into a clinical perspective such in vitro evidences, we then performed histological analysis on bone biopsies obtained from MM patients, MGUS and healthy controls. We found a significant reduction in the number of viable osteocytes in MM patients as compared to controls. A significant negative correlation between the number of viable osteocytes and that of osteoclasts was also demonstrated. Moreover, as regards the skeletal involvement, we found that MM patients with bone lesions have a significant lower number of viable osteocyte than those without. Overall, our data suggest a role of osteocytic cell death in MM-induced osteoclast formation in vitro and MM bone disease in vivo in MM patients. This series of microarray experiments contains the gene expression profiles of HOB-01 osteocytes cultured alone and co-cultured with the JJN3 human myeloma cell line. 5 micrograms of total RNA was processed, and in accordance with the manufacturer's protocols, the fragmented biotin-labelled cRNA were hybridized on GeneChip Human Genome U133 Plus 2.0 Arrays (Affymetrix Inc.). The arrays were scanned using the Agilent GeneChip Scanner 3000 7G. The images were acquired using Affymetrix GeneChip Operating System (GCOS) 1.1 software and the probe level data converted to expression values using default GCOS1.1 scaling. Natural-scaled data are provided.

ORGANISM(S): Homo sapiens

SUBMITTER: Antonino Neri 

PROVIDER: E-GEOD-27372 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress