title: LIGHT/TNFSF14 increases osteoclastogenesis and decreases osteoblastogenesis in multiple myeloma-bone disease.
abstract: LIGHT, a TNF superfamily member, is involved in T-cell homeostasis and erosive bone disease associated with rheumatoid arthritis. Herein, we investigated whether LIGHT has a role in Multiple Myeloma (MM)-bone disease. We found that LIGHT was overproduced by CD14+ monocytes, CD8+ T-cells and neutrophils of peripheral blood and bone marrow (BM) from MM-bone disease patients. We also found that LIGHT induced osteoclastogenesis and inhibited osteoblastogenesis. In cultures from healthy-donors, LIGHT induced osteoclastogenesis in RANKL-dependent and -independent manners. In the presence of a sub-optimal RANKL concentration, LIGHT and RANKL synergically stimulated osteoclast formation, through the phosphorylation of Akt, NFκB and JNK pathways. In cultures of BM samples from patients with bone disease, LIGHT inhibited the formation of CFU-F and CFU-OB as well as the expression of osteoblastic markers including collagen-I, osteocalcin and bone sialoprotein-II. LIGHT indirectly inhibited osteoblastogenesis in part through sclerostin expressed by monocytes. In conclusion, our findings for the first time provide evidence for a role of LIGHT in MM-bone disease development.
authors.affiliation: Department of Basic and Medical Sciences, Neurosciences and Sense Organs, Section of Human Anatomy and Histology, University of Bari, Bari, Italy.
authors.forename: Giacomina
authors.initials: G
authors.lastname: Brunetti
authors.affiliation: Department of Emergency and Organ Transplantation, Section of Hematology with Transplantation, University of Bari, Bari, Italy.
authors.forename: Rita
authors.initials: R
authors.lastname: Rizzi
authors.affiliation: Department of Basic and Medical Sciences, Neurosciences and Sense Organs, Section of Human Anatomy and Histology, University of Bari, Bari, Italy.
authors.forename: Angela
authors.initials: A
authors.lastname: Oranger
authors.affiliation: Department of Basic and Medical Sciences, Neurosciences and Sense Organs, Section of Human Anatomy and Histology, University of Bari, Bari, Italy.
authors.forename: Isabella
authors.initials: I
authors.lastname: Gigante
authors.affiliation: Department of Clinical and Experimental Medicine, University of Foggia, Foggia, Italy.
authors.forename: Giorgio
authors.initials: G
authors.lastname: Mori
authors.affiliation: Department of Basic and Medical Sciences, Neurosciences and Sense Organs, Section of Human Anatomy and Histology, University of Bari, Bari, Italy.
authors.forename: Grazia
authors.initials: G
authors.lastname: Taurino
authors.affiliation: Department of Basic and Medical Sciences, Neurosciences and Sense Organs, Section of Human Anatomy and Histology, University of Bari, Bari, Italy.
authors.forename: Teresa
authors.initials: T
authors.lastname: Mongelli
authors.affiliation: Department of Basic and Medical Sciences, Neurosciences and Sense Organs, Section of Human Anatomy and Histology, University of Bari, Bari, Italy.
authors.forename: Graziana
authors.initials: G
authors.lastname: Colaianni
authors.affiliation: Department of Basic and Medical Sciences, Neurosciences and Sense Organs, Section of Human Anatomy and Histology, University of Bari, Bari, Italy.
authors.forename: Adriana
authors.initials: A
authors.lastname: Di Benedetto
authors.affiliation: Department of Basic and Medical Sciences, Neurosciences and Sense Organs, Section of Human Anatomy and Histology, University of Bari, Bari, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Tamma
authors.affiliation: Department of Emergency and Organ Transplantation, University of Bari, Bari, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Ingravallo
authors.affiliation: Department of Emergency and Organ Transplantation, University of Bari, Bari, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Napoli
authors.affiliation: Department of Biomedical Sciences and Human Oncology, University of Bari, Bari, Italy.
authors.forename: Maria Felicia
authors.initials: MF
authors.lastname: Faienza
authors.affiliation: Department of Emergency and Organ Transplantation, Section of Hematology with Transplantation, University of Bari, Bari, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Mestice
authors.affiliation: Department of Emergency and Organ Transplantation, Section of Hematology with Transplantation, University of Bari, Bari, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Curci
authors.affiliation: Department of Emergency and Organ Transplantation, Section of Hematology with Transplantation, University of Bari, Bari, Italy.
authors.forename: Giorgina
authors.initials: G
authors.lastname: Specchia
authors.affiliation: Department of Basic and Medical Sciences, Neurosciences and Sense Organs, Section of Human Anatomy and Histology, University of Bari, Bari, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Colucci
authors.affiliation: Department of Basic and Medical Sciences, Neurosciences and Sense Organs, Section of Human Anatomy and Histology, University of Bari, Bari, Italy.
authors.forename: Maria
authors.initials: M
authors.lastname: Grano
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001847:Bone Diseases / Q000378:metabolism / Q000473:pathology*; D016022:Case-Control Studies; D002454:Cell Differentiation / Q000502:physiology; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000378:metabolism / Q000473:pathology*; D010006:Osteoblasts / Q000378:metabolism / Q000473:pathology*; D010010:Osteoclasts / Q000378:metabolism / Q000473:pathology*; D053326:Tumor Necrosis Factor Ligand Superfamily Member 14 / Q000096:biosynthesis* / Q000235:genetics
chemical_list: C505914:TNFSF14 protein, human; D053326:Tumor Necrosis Factor Ligand Superfamily Member 14