title: Increased osteocyte death in multiple myeloma patients: role in myeloma-induced osteoclast formation.
abstract: The involvement of osteocytes in multiple myeloma (MM)-induced osteoclast (OCL) formation and bone lesions is still unknown. Osteocytes regulate bone remodelling at least partially, as a result of their cell death triggering OCL recruitment. In this study, we found that the number of viable osteocytes was significantly smaller in MM patients than in healthy controls, and negatively correlated with the number of OCLs. Moreover, the MM patients with bone lesions had a significantly smaller number of viable osteocytes than those without, partly because of increased apoptosis. These findings were further confirmed by ultrastructural in vitro analyses of human preosteocyte cells cocultured with MM cells, which showed that MM cells increased preosteocyte death and apoptosis. A micro-array analysis showed that MM cells affect the transcriptional profiles of preosteocytes by upregulating the production of osteoclastogenic cytokines such as interleukin (IL)-11, and increasing their pro-osteoclastogenic properties. Finally, the osteocyte expression of IL-11 was higher in the MM patients with than in those without bone lesions. Our data suggest that MM patients are characterized by a reduced number of viable osteocytes related to the presence of bone lesions, and that this is involved in MM-induced OCL formation.
authors.affiliation: Department of Internal Medicine and Biomedical Science, Hematology and Bone Marrow Transplantation Center, University of Parma, Parma, Italy. N_giuliani@yahoo.com
authors.forename: N
authors.initials: N
authors.lastname: Giuliani
authors.forename: M
authors.initials: M
authors.lastname: Ferretti
authors.forename: M
authors.initials: M
authors.lastname: Bolzoni
authors.forename: P
authors.initials: P
authors.lastname: Storti
authors.forename: M
authors.initials: M
authors.lastname: Lazzaretti
authors.forename: B
authors.initials: B
authors.lastname: Dalla Palma
authors.forename: S
authors.initials: S
authors.lastname: Bonomini
authors.forename: E
authors.initials: E
authors.lastname: Martella
authors.forename: L
authors.initials: L
authors.lastname: Agnelli
authors.forename: A
authors.initials: A
authors.lastname: Neri
authors.forename: F
authors.initials: F
authors.lastname: Ceccarelli
authors.forename: C
authors.initials: C
authors.lastname: Palumbo
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D015153:Blotting, Western; D001862:Bone Resorption; D016022:Case-Control Studies; D002454:Cell Differentiation; D002478:Cells, Cultured; D018920:Coculture Techniques; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D007124:Immunoenzyme Techniques; D020287:In Situ Nick-End Labeling; D017370:Interleukin-11 / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D008998:Monoclonal Gammopathy of Undetermined Significance / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D009101:Multiple Myeloma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D020411:Oligonucleotide Array Sequence Analysis; D010010:Osteoclasts / Q000378:metabolism / Q000473:pathology*; D010011:Osteocytes / Q000378:metabolism / Q000473:pathology*; D010012:Osteogenesis / Q000502:physiology; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D014408:Biomarkers, Tumor; D017370:Interleukin-11; D012333:RNA, Messenger