gp130 CYTOKINE FAMILY AND BONE CELLS

Heymann, Dominique; Rousselle, Anne-Valérie

doi:10.1006/cyto.2000.0747

Cited by 168 publications

(121 citation statements)

References 209 publications

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“…IL-6 and IL-11 play an important role in osteoclast development, such as promoting osteoclastogenesis and bone resorption in bone marrow cultures. 16,17 IL-6 and IL-11 are capable of inducing osteoclast formation from peripheral blood mononuclear cells by a receptor activator of nuclear factor-kB ligand-independent mechanism. 18 IL-11 is produced by fibroblasts, mesenchyme-derived stromal cells of bone marrow, osteoblasts and chondrocytes.…”

Section: Discussionmentioning

confidence: 99%

De novo 19q13.42 duplications involving NLRP gene cluster in a patient with systemic-onset juvenile idiopathic arthritis

et al. 2011

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Systemic-onset juvenile idiopathic arthritis (s-JIA) is a rare inflammatory disease classified as a subtype of chronic childhood arthritis, manifested by spiking fever, erythematous skin rash, pericarditis and hepatosplenomegaly. The genetic background underlying s-JIA remains poorly understood. To detect disease-related copy number variations (CNVs), we performed singlenucleotide polymorphism array analysis in 50 patients with s-JIA. We detected many CNVs, but most of them were inherited from either of normal-phenotype parents. However, in one patient, we could identify two de novo microduplications at 19q13.42 with the size of 77 and 622 kb, separated by a 109-kb segment of normal copy number. The duplications encompass NLRP family (NLRP2, NLRP9 and NLRP11) as well as IL11 and HSPBP1, all of which have an important role in inflammatory pathways. These genes may significantly contribute to the pathogenesis of s-JIA.

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Section: Discussionmentioning

confidence: 99%

De novo 19q13.42 duplications involving NLRP gene cluster in a patient with systemic-onset juvenile idiopathic arthritis

et al. 2011

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“…Primary cultured mice osteoblastic cells were cultured in a-MEM containing 10% FBS and PCSM with 10 nM 1a,25-dihydroxyvitamin D 3 [1,25(OH) 2 D 3 ; Sigma, St. Louis, MO, USA] and 100 nM dexamethasone (Dex; Sigma) for 72 hours before fixation. Cells were fixed with formaldehyde, permeabilized with Triton X-100, and then subjected to immunostaining using goat anti-RANKL antibody (Santa Cruz Biotechnology, Santa Cruz, CA, USA), rabbit anti-LAMP1 antibody (Sigma), or mouse anti-58K Golgi protein antibody (Abcam, Cambridge, UK) as the primary antibody, and the corresponding secondary antibodies were labeled with Alexa Fluor dye (Invitrogen) diluted in Can Get Signal immunostain (Toyobo, Osaka, Japan).…”

Section: Immunostaining and Observation Of Live Cellsmentioning

confidence: 99%

“…The equilibrium between osteoblast and osteoclast activities is tightly regulated by many factors such as hormones, growth factors, and cytokines. (1,2) Excess activation of osteoclasts disturbs this equilibrium and culminates in bone destruction, (3) which is a common mechanism for the development of osteopenic disorders, including postmenopausal osteoporosis, rheumatoid arthritis, and lytic bone metastases. (4,5) Numerous studies have shown that the receptor activator of NF-kB (RANK) signaling pathway is crucial for the differentiation and activation of osteoclasts.…”

Section: Introductionmentioning

confidence: 99%

Function of OPG as a traffic regulator for RANKL is crucial for controlled osteoclastogenesis

Aoki

Honma

Kariya

et al. 2010

Journal of Bone and Mineral Research

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The amount of the receptor activator of NF-kB ligand (RANKL) on the osteoblastic cell surface is considered to determine the magnitude of the signal input to osteoclast precursors and the degree of osteoclastogenesis. Previously, we have shown that RANKL is localized predominantly in lysosomal organelles, but little is found on the osteoblastic cell surface, and consequently, the regulated subcellular trafficking of RANKL in osteoblastic cells is important for controlled osteoclastogenesis. Here we have examined the involvement of osteoprotegerin (OPG), which is currently recognized as a decoy receptor for RANKL, in the regulation of RANKL behavior. It was suggested that OPG already makes a complex with RANKL in the Golgi apparatus and that the complex formation is necessary for RANKL sorting to the secretory lysosomes. It was also shown that each structural domain of OPG is indispensable for exerting OPG function as a traffic regulator. In particular, the latter domains of OPG, whose physiologic functions have been unclear, were indicated to sort RANKL molecules to lysosomes from the Golgi apparatus. In addition, the overexpression of RANK-OPG chimeric protein, which retained OPG function as a decoy receptor but lost the function as a traffic regulator, inhibited endogenous OPG function as a traffic regulator selectively in osteoblastic cells and resulted in the upregulation of osteoclastogenic ability despite the increased number of decoy receptor molecules. Conclusively, OPG function as a traffic regulator for RANKL is crucial for regulating osteoclastogenesis at least as well as that as a decoy receptor. ß

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“…(1,2) The coordinated cycle of osteoclast bone resorption and osteoblast bone formation is requisite for maintaining these bone functions. (1) The equilibrium of osteoclast and osteoblast activity is tightly regulated, (3,4) and excessive osteoclast activation disturbs this equilibrium and culminates in osteopenic disorders. (5) Numerous studies, including detailed in vitro analyses and in vivo genetic investigations, have revealed that the receptor activator of the NF-kB (RANK) signaling is crucial for differentiation and activation of osteoclasts.…”

Section: Introductionmentioning

confidence: 99%

Rab27a and Rab27b are involved in stimulation-dependent RANKL release from secretory lysosomes in osteoblastic cells

Kariya

Honma

Hanamura

et al. 2010

Journal of Bone and Mineral Research

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The quantity of the receptor activator of NF-kB ligand (RANKL) expressed at the cell surface of osteoblastic cells is an important factor regulating osteoclast activation. Previously, RANKL was found to be localized to secretory lysosomes in osteoblastic cells and to translocate to the cell surface in response to stimulation with RANK-Fc-conjugated beads. However, the in vivo significance of stimulation-dependent RANKL release has not been elucidated. In this study we show that small GTPases Rab27a and Rab27b are involved in the stimulation-dependent RANKL release pathway in osteoblastic cells. Suppression of either Rab27a or Rab27b resulted in a marked reduction in RANKL release after stimulation. Slp4-a, Slp5, and Munc13-4 acted as effector molecules that coordinated Rab27a/b activity in this pathway. Suppression of Rab27a/b or these effector molecules did not inhibit accumulation of RANKL in lysosomal vesicles around the stimulated sites but did inhibit the fusion of these vesicles to the plasma membrane. In osteoblastic cells, suppression of the effector molecules resulted in reduced osteoclastogenic ability. Furthermore, Jinx mice, which lack a functional Munc13-4 gene, exhibited a phenotype characterized by increased bone volume near the tibial metaphysis caused by low bone resorptive activity. In conclusion, stimulation-dependent RANKL release is mediated by Rab27a/b and their effector molecules, and this mechanism may be important for osteoclast activation in vivo. ß

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gp130 CYTOKINE FAMILY AND BONE CELLS

Cited by 168 publications

References 209 publications

De novo 19q13.42 duplications involving NLRP gene cluster in a patient with systemic-onset juvenile idiopathic arthritis

De novo 19q13.42 duplications involving NLRP gene cluster in a patient with systemic-onset juvenile idiopathic arthritis

Function of OPG as a traffic regulator for RANKL is crucial for controlled osteoclastogenesis

Rab27a and Rab27b are involved in stimulation-dependent RANKL release from secretory lysosomes in osteoblastic cells

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