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An age-dependent interaction with leptin unmasks ghrelin's bone-protective effects

Academic Article
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Overview

authors

  • van der Velde, M.
  • van der Eerden, B. C. J.
  • Sun, Y. X.
  • Almering, J. M. M.
  • van der Lely, A. J.
  • Delhanty, P. J. D.
  • Smith, Roy
  • van Leeuwen, J. P. T. M.

publication date

  • August 2012

journal

  • Endocrinology  Journal

abstract

  • The mutual interplay between energy homeostasis and bone metabolism is an important emerging concept. Ghrelin and leptin antagonize each other in regulating energy balance, but the role of this interaction in bone metabolism is unknown. Using ghrelin receptor and leptin-deficient mice, we show that ghrelin has dual effects on osteoclastogenesis, inhibiting osteoclast progenitors directly and stimulating osteoclastogenesis via a more potent systemic/central pathway. Using mice with combined ghrelin receptor and leptin deficiency, we find that this systemic osteoclastogenic activity is suppressed by leptin, thus balancing the two counterregulatory ghrelin pathways and leading to an unchanged bone structure. With aging, this osteoclastogenic ghrelin pathway is lost, unmasking the direct protective effect of ghrelin on bone structure. In conclusion, we identify a novel regulatory network linking orexigenic and anorectic metabolic factors with bone metabolism that is age dependent.

subject areas

  • Age Factors
  • Animals
  • Bone Resorption
  • Bone and Bones
  • Ghrelin
  • Leptin
  • Male
  • Mice
  • Mice, Knockout
  • Osteoclasts
  • Osteogenesis
  • Real-Time Polymerase Chain Reaction
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Identity

International Standard Serial Number (ISSN)

  • 0013-7227

Digital Object Identifier (DOI)

  • 10.1210/en.2012-1277

PubMed ID

  • 22700774
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Additional Document Info

start page

  • 3593

end page

  • 3602

volume

  • 153

issue

  • 8

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