Plasma cells release membrane microparticles in a mouse model of multiple myeloma.

Microparticles (MPs) released from the plasma membrane play a role in tumor progression. Involvement of MPs in myeloma (MM) has been poorly investigated. Because of the strong interaction of MM cells with bone microenvironment, we hypothesized an implication of MPs in MM using a murine model. Forty-four mice were injected with 5THL-MM cells and compared with 14 non-injected mice. Blood was collected at the early and end stages of MM development (EMM and LMM) to characterize the circulating MPs. At LMM, MPs were isolated from bone marrow (BM) of long bones of 22 mice, after centrifugation. Electron microscopy immunohistochemistry and Western blotting using CD138 were performed on BM-derived MPs. At EMM, MPs circulating level was significantly lower versus controls. In LMM, a significant increase of the total MP number from plasma was observed versus controls. Characterization of circulating MPs showed an increase of leukocyte- and erythrocyte-derived MPs. In LMM, serum M-protein was correlated with circulating MP number. BM-derived MPs increased in LMM and expressed CD138. Anti-CD138 coupled with nanobeads localized at the MP surface. There is evidence of an association between increase of MPs and MM development; the results underscore the participation of plasma cell-derived MPs originating from BM.

Thiazolidinediones cause compaction of nuclear heterochromatin in the pluripotent mesenchymal cell line C3H10T1/2 when inducing an adipogenic phenotype.

OBJECTIVE: To characterize the nuclear changes induced in vitro by thiazolidinediones (TZDs) in a murine pluripotent mesenchymal cell line. STUDY DESIGN: The C3H10T1/2 cell line, which can differentiate either in osteoblast or in adipocyte, was cultured in the presence of pioglitazone (5 microM) or rosiglitazone (0.5 microM) for 6, 8 and 9 days (D). Quantitative real-time polymerase chain reaction analysis evaluated the expression of key genes of the adipocytic or osteoblastic differentiation (PPARgamma[peroxisome proliferatoractivated receptor gamma], Runx2 [runt-related transcription factor 2] and alkaline phosphatase). Cells were stained with Oil Red O for lipids, and chromatin was counter-stained with hematoxylin. Cells were photographed at x 1,000 magnification and analyzed with texture analysis software. Nuclear area, mean gray level and run-length parameters were calculated. RESULTS: PPARgamma was significantly expressed from D6 (normalized ratio > 7) in TZD groups (ratio >27 at D9). No significant differences were found for either Runx2 or alkaline phosphatase expression versus control at D6 or D9. Cells cultured with TZDs began to differentiate into adipocytes with numerous lipid droplets which appeared at D6. Nuclear area decreased suddenly at D6 for both TZDs, and the mean gray level increased. Run-length parameters changed significantly due to chromatin compaction. CONCLUSION: TZDs provoked differentiation of C3H10T1/2 into adipocytes, leading to inactivation of genes that were highly compacted into heterochromatin.

Texture analysis of computed tomographic images in osteoporotic patients with sinus lift bone graft reconstruction.

OBJECTIVE: Bone implants are now widely used to replace missing teeth. Bone grafting (sinus lift) is a very useful way to increase the bone volume of the maxilla in patients with bone atrophy. There is a 6- to 9-month delay for the receiver grafted site to heal before the implants can be placed. Computed tomography is a useful method to measure the amount of remaining bone before implantation and to evaluate the quality of the receiver bone at the end of the healing period. Texture analysis is a non-invasive method useful to characterize bone microarchitecture on X-ray images. PATIENTS AND METHODS: Ten patients in which a sinus lift surgery was necessary before implantation were analyzed in the present study. All had a bone reconstruction with a combination of a biomaterial (beta tricalcium phosphate) and autograft bone harvested at the chin. Computed tomographic images were obtained before grafting (t0), at mid-interval (t1, 4.2 ± 0.7 months) and before implant placement (t2, 9.2 ± 0.6 months). Texture analysis was done with the run-length method. RESULTS: A significant increase of texture parameters at t1 reflected a gain of homogeneity due to the graft and the beginning of bone remodeling. At t2, some parameters remained high and corresponded to the persistence of bone trabeculae while the resorption of biomaterials was identified by other parameters which tended to return to pregraft values. CONCLUSION: Texture analysis identified changes during the healing of the receiver site. CLINICAL RELEVANCE: The method is known to correlate with microarchitectural changes in bone and could be a useful approach to characterized osseointegrated grafts.