GLORIA

GEOMAR Library Ocean Research Information Access

X

Your email was sent successfully. Check your inbox.

An error occurred while sending the email. Please try again.

Proceed reservation?

Export
Filter
  • Nishikawa, Keizo  (2)
  • Medicine  (2)
  • 1
    Online Resource
    Online Resource
    Folliculin Regulates Osteoclastogenesis Through Metabolic Regulation
    Oxford University Press (OUP) ; 2018
    In:  Journal of Bone and Mineral Research Vol. 33, No. 10 ( 2018-10-01), p. 1785-1798
    Details
    In: Journal of Bone and Mineral Research, Oxford University Press (OUP), Vol. 33, No. 10 ( 2018-10-01), p. 1785-1798
    Abstract: Osteoclast differentiation is a dynamic differentiation process, which is accompanied by dramatic changes in metabolic status as well as in gene expression. Recent findings have revealed an essential connection between metabolic reprogramming and dynamic gene expression changes during osteoclast differentiation. However, the upstream regulatory mechanisms that drive these metabolic changes in osteoclastogenesis remain to be elucidated. Here, we demonstrate that induced deletion of a tumor suppressor gene, Folliculin (Flcn), in mouse osteoclast precursors causes severe osteoporosis in 3 weeks through excess osteoclastogenesis. Flcn-deficient osteoclast precursors reveal cell autonomous accelerated osteoclastogenesis with increased sensitivity to receptor activator of NF-κB ligand (RANKL). We demonstrate that Flcn regulates oxidative phosphorylation and purine metabolism through suppression of nuclear localization of the transcription factor Tfe3, thereby inhibiting expression of its target gene Pgc1. Metabolome studies revealed that Flcn-deficient osteoclast precursors exhibit significant augmentation of oxidative phosphorylation and nucleotide production, resulting in an enhanced purinergic signaling loop that is composed of controlled ATP release and autocrine/paracrine purinergic receptor stimulation. Inhibition of this purinergic signaling loop efficiently blocks accelerated osteoclastogenesis in Flcn-deficient osteoclast precursors. Here, we demonstrate an essential and novel role of the Flcn-Tfe3-Pgc1 axis in osteoclastogenesis through the metabolic reprogramming of oxidative phosphorylation and purine metabolism. © 2018 The Authors Journal of Bone and Mineral Research published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research (ASBMR).
    Type of Medium: Online Resource
    ISSN: 0884-0431 , 1523-4681
    URL: Article
    DOI: 10.1002/jbmr.3477
    RVK:
    XA 52230
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2018
    detail.hit.zdb_id: 2008867-X
    detail.hit.zdb_id: 632783-7
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 2
    Online Resource
    Online Resource
    MafB interacts with Gcm2 and regulates parathyroid hormone expression and parathyroid development
    Oxford University Press (OUP) ; 2011
    In:  Journal of Bone and Mineral Research Vol. 26, No. 10 ( 2011-10-01), p. 2463-2472
    Details
    In: Journal of Bone and Mineral Research, Oxford University Press (OUP), Vol. 26, No. 10 ( 2011-10-01), p. 2463-2472
    Abstract: Serum calcium and phosphate homeostasis is critically regulated by parathyroid hormone (PTH) secreted by the parathyroid glands. Parathyroid glands develop from the bilateral parathyroid-thymus common primordia. In mice, the expression of transcription factor Glial cell missing 2 (Gcm2) begins in the dorsal/anterior part of the primordium on embryonic day 9.5 (E9.5), specifying the parathyroid domain. The parathyroid primordium then separates from the thymus primordium and migrates to its adult location beside the thyroid gland by E15.5. Genetic ablation of gcm2 results in parathyroid agenesis in mice, indicating that Gcm2 is essential for early parathyroid organogenesis. However, the regulation of parathyroid development at later stages is not well understood. Here we show that transcriptional activator v-maf musculoaponeurotic fibrosarcoma oncogene homologue B (MafB) is developmentally expressed in parathyroid cells after E11.5. MafB expression was lost in the parathyroid primordium of gcm2 null mice. The parathyroid glands of mafB+/− mice were mislocalized between the thymus and thyroid. In mafB−/− mice, the parathyroid did not separate from the thymus. Furthermore, in mafB−/− mice, PTH expression and secretion were impaired; expression levels of renal cyp27b1, one of the target genes of PTH, was decreased; and bone mineralization was reduced. We also demonstrate that although Gcm2 alone does not stimulate the PTH gene promoter, it associates with MafB to synergistically activate PTH expression. Taken together, our results suggest that MafB regulates later steps of parathyroid development, that is, separation from the thymus and migration toward the thyroid. MafB also regulates the expression of PTH in cooperation with Gcm2. © 2011 American Society for Bone and Mineral Research
    Type of Medium: Online Resource
    ISSN: 0884-0431 , 1523-4681
    URL: Article
    DOI: 10.1002/jbmr.458
    RVK:
    XA 52230
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2011
    detail.hit.zdb_id: 2008867-X
    detail.hit.zdb_id: 632783-7
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
Close ⊗
This website uses cookies and the analysis tool Matomo. More information can be found here...