Estrogen receptor-α expression in neuronal cells affects bone mass

Claes Ohlsson, Cecilia Engdahl, Anna Borjesson, Sara H Windahl, Erik Studer, Lars Westberg, Elias Eriksson, Antti Koskela, Juha Tuukkanen, Andree Krust, Pierre Chambon, Hans Carlsten, Marie K Lagerquist

Research output: Contribution to journalArticlepeer-review

Abstract

It has generally been assumed that bone mass is controlled by endocrine mechanisms and the local bone environment. Recent findings demonstrate that central pathways are involved in the regulation of bone mass. Estrogen is involved in the regulation of bone homeostasis and the CNS is also a target for estrogen actions. The aim of this study was to investigate in vivo the role of central estrogen receptor-α (ERα) expression for bone mass. Nestin-Cre mice were crossed with ERα(flox) mice to generate mice lacking ERα expression specifically in nervous tissue (nestin-ERα(-/-)). Bone mineral density was increased in both the trabecular and cortical bone compartments in nestin-ERα(-/-) mice compared with controls. Femoral bone strength was increased in nestin-ERα(-/-) mice, as demonstrated by increased stiffness and maximal load of failure. The high bone mass phenotype in nestin-ERα(-/-) mice was mainly caused by increased bone formation. Serum leptin levels were elevated as a result of increased leptin expression in white adipose tissue (WAT) and slightly increased amount of WAT in nestin-ERα(-/-) mice. Leptin receptor mRNA levels were reduced in the hypothalamus but not in bone. In conclusion, inactivation of central ERα signaling results in increased bone mass, demonstrating that the balance between peripheral stimulatory and central inhibitory ERα actions is important for the regulation of bone mass. We propose that the increased bone mass in nestin-ERα(-/-) mice is mediated via decreased central leptin sensitivity and thereby increased secretion of leptin from WAT, which, in turn, results in increased peripheral leptin-induced bone formation.
Original languageEnglish
Pages (from-to)983-988
Number of pages6
JournalProceedings of the National Academy of Sciences
Volume109
Issue number3
DOIs
Publication statusPublished - 17 Jan 2012

Keywords

  • Animals
  • Bone Density
  • Bone Remodeling
  • Bone and Bones
  • Estrogen Receptor alpha
  • Female
  • Follicle Stimulating Hormone
  • Gene Deletion
  • Intermediate Filament Proteins
  • Leptin
  • Luteinizing Hormone
  • Mice
  • Nerve Tissue Proteins
  • Neurons
  • Organ Size
  • Ovariectomy
  • Serotonin
  • Signal Transduction
  • Steroids
  • T-Lymphocytes

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