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Repression of osteoblast maturation by ERRα accounts for bone loss induced by estrogen deficiency

Marlène Gallet1, Soraya Saïdi, Eric Haÿ

  • 1Institut de Génomique Fonctionnelle de Lyon, Université de Lyon, Centre national de la recherche scientifique UMR5242, Ecole Normale Supérieure de Lyon, Lyon, France.

Plos One
|January 30, 2013
PubMed

Insights

Estrogen-related receptor alpha (ERRα) inactivation prevents bone loss in mice by promoting osteoblast maturation. This finding highlights ERRα

Area of Science:

  • Endocrinology
  • Bone Biology
  • Molecular Biology

Background:

  • Estrogen-related receptor alpha (ERRα) is an orphan nuclear receptor implicated in bone metabolism.
  • Complete ERRα inactivation confers resistance to age-related and estrogen withdrawal-induced bone loss in mice.
  • ERRα negatively regulates osteoblast differentiation and maturation.

Purpose of the Study:

  • To investigate whether ERRα's regulation of osteoblast maturation contributes to bone loss.
  • To determine the specific role of ERRα in estrogen deficiency-induced bone loss.

Main Methods:

  • Generation of conditional knockout mice (ERRα cKO) with targeted ERRα inactivation during osteoblast maturation.
  • Assessment of bone aging and bone loss following ovariectomy in ERRα cKO mice and controls.

Main Results:

  • Bone aging was unaffected in ERRα cKO mice compared to controls.
  • ERRα cKO mice were completely resistant to ovariectomy-induced bone loss.
  • ERRα inactivation specifically impacts late-stage osteoblast maturation, not early commitment.

Conclusions:

  • The late-acting negative effects of ERRα on osteoblast maturation, not early commitment, are responsible for reduced bone mineral density during estrogen deficiency.
  • Targeting ERRα's role in osteoblast maturation may offer therapeutic strategies for postmenopausal osteoporosis.

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