Cellular activity and signaling induced by osteoprotegerin in osteoclasts: involvement of receptor activator of nuclear factor κB ligand and MAPK

Théoleyre, Sandrine; Wittrant, Yohann; Couillaud, Séverine; Vusio, Patricia; Berreur, Martine; Dunstan, Colin R.; Blanchard, Frédéric; Rédini, Françoise; Heymann, Dominique

doi:10.1016/j.bbamcr.2003.10.005

Cited by 44 publications

(31 citation statements)

References 22 publications

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“…On the other hand, when recombinant RANK-CRD-OPG-DCRD protein was added to the medium, little clustering of RANKL at the plasma membrane was observed (data not shown), indicating that the property as a cross-linker for RANKL is much weaker in this chimeric protein. A previous report showing that the binding sites of RANKL to RANK and RANKL to OPG are somewhat different from each other (37) also supports the preceding observation. In addition, we also investigated the interaction between OPG and Vps33a because we have previously shown the involvement of Vps33a in the transfer of newly synthesized RANKL to the lysosomes in osteoblastic cells.…”

Section: Discussionsupporting

confidence: 84%

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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Section: Discussionsupporting

confidence: 84%

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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“…(25) Histochemical staining for tartaric acidresistant alkaline phosphatase (ALP) showed that, after a…”

Section: Culturing Of Primary Osteoblastic Cells Bone Marrow Osteoprmentioning

confidence: 99%

Ubiquitin Ligase Cbl-b Downregulates Bone Formation Through Suppression of IGF-I Signaling in Osteoblasts During Denervation

Suzue

Nikawa

Onishi

et al. 2006

Journal of Bone and Mineral Research

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Unloading can prevent bone formation by osteoblasts. To study this mechanism, we focused on a ubiquitin ligase, Cbl-b, which was highly expressed in osteoblastic cells during denervation. Our results suggest that Cbl-b may mediate denervation-induced osteopenia by inhibiting IGF-I signaling in osteoblasts.Introduction: Unloading, such as denervation (sciatic neurectomy) and spaceflight, suppresses bone formation by osteoblasts, leading to osteopenia. The resistance of osteoblasts to growth factors contributes to such unloading-mediated osteopenia. However, a detailed mechanism of this resistance is unknown. We first found that a RING-type ubiquitin ligase, Cbl-b, was highly expressed in osteoblastic cells after sciatic neurectomy in mice. In this study, we reasoned that Cbl-b played an important role in the resistance of osteoblasts to IGF-I. Materials and Methods: Cbl-b-deficient (Cbl-b

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“…45,46 Osteoprotegerin promotes MMP activity both directly and indirectly (i.e., by stabilizing RANKL activity). 45,47,48 The role of OPG in calcium homeostasis could also be pathophysiologically relevant. Calcium signals regulate OPG expression, 49,50 and a calcium antagonist traditionally used to prevent cardiovascular disease was recently found to have neuroprotective effects.…”

Section: Discussionmentioning

confidence: 99%

Osteoprotegerin levels in patients with severe mental disorders

Hope

Melle²,

Aukrust³

et al. 2010

jpn

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Background: Severe mental disorders are associated with elevated levels of inflammatory markers. In the present study, we investigated whether osteoprotegerin (OPG), a member of the tumour necrosis factor receptor family involved in calcification and inflammation, is elevated in patients with severe mental disorders. Methods: We measured the plasma levels of OPG in patients with severe mental disorders (n = 312; 125 with bipolar disorder and 187 with schizophrenia) and healthy volunteers (n = 239). Results: The mean plasma levels of OPG were significantly higher in patients than in controls (t 531 = 2.6, p = 0.01), with the same pattern in bipolar disorder and schizophrenia. The increase was significant after adjustment for possible confounding variables, including age, sex, ethnic background, alcohol consumption, liver and kidney function, diabetes, cardiovascular disease, autoimmune diseases and levels of cholesterol, glucose and C-reactive protein. Limitations: Owing to the cross-sectional design, it is difficult to determine causality. Conclusion: Our results indicate that elevated OPG levels are associated with severe mental disorders and suggest that mechanisms related to calcification and inflammation may play a role in disease development.

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Cellular activity and signaling induced by osteoprotegerin in osteoclasts: involvement of receptor activator of nuclear factor κB ligand and MAPK

Cited by 44 publications

References 22 publications

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

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

Ubiquitin Ligase Cbl-b Downregulates Bone Formation Through Suppression of IGF-I Signaling in Osteoblasts During Denervation

Osteoprotegerin levels in patients with severe mental disorders

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