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Long-term selective estrogen receptor-beta agonist treatment modulates gene expression in bone and bone marrow of

Bernadett Balla1, Miklós Sárvári2, János P Kósa1

  • 11st Department of Internal Medicine, Semmelweis University, Budapest, Hungary.

The Journal of Steroid Biochemistry and Molecular Biology
|January 28, 2019
PubMed

Insights

Ovariectomy (OVX) significantly altered gene expression in bone and bone marrow. Estrogen receptor beta (ERβ) agonist DPN partially restored some OVX-induced changes, highlighting ERβ

Area of Science:

  • Endocrinology
  • Skeletal Biology
  • Molecular Biology

Background:

  • Gonadal hormones, like 17β-estradiol, are crucial for skeletal homeostasis.
  • The specific roles of ovarian hormone deficiency and estrogen receptor beta (ERβ) in bone and bone marrow remain incompletely understood.

Purpose of the Study:

  • To investigate gene expression changes in bone and bone marrow following ovariectomy (OVX).
  • To evaluate the effects of long-term ERβ agonist, diarylpropionitrile (DPN), on these gene expression alterations.

Main Methods:

  • Gene expression analysis in femoral bone and bone marrow after OVX in a mouse model.
  • Administration of the ERβ agonist DPN to assess its modulatory effects.
  • Canonical variates analysis (CVA) to identify affected signaling pathways.

Main Results:

  • OVX induced widespread gene expression changes in both bone (20/22 genes upregulated) and bone marrow (25/37 genes upregulated).
  • DPN treatment partially restored 10 OVX-induced gene expression changes in bone, indicating a modulatory role for ERβ.
  • DPN had a modest effect in bone marrow, restoring only 2 gene expressions, though the PI3K/Akt pathway was significantly impacted in both tissues.

Conclusions:

  • ERβ plays a significant role in modulating bone physiology and gene expression within the bone microenvironment.
  • The bone marrow is highly responsive to gonadal hormones, with distinct responses to ERβ agonism compared to bone tissue.
  • These findings enhance understanding of ERβ-mediated gene expression alterations in bone and bone marrow niches.
Keywords:
BoneOvariectomyRatSelective estrogen receptor beta agonistTranscription

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