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Oestrogen-activated autophagy has a negative effect on the anti-osteoclastogenic function of oestrogen

Liang Cheng1, Yunrong Zhu2, Dianshan Ke1

  • 1Guangdong Provincial Key Laboratory of Bone and Joint Degeneration Diseases, The Third Affiliated Hospital of Southern Medical University, Guangzhou, China.

Cell Proliferation
|March 12, 2020
PubMed
Abstract

Insights

Oestrogen enhances osteoclast precursor autophagy, which paradoxically inhibits its bone-protective effects. Autophagy inhibition may boost oestrogen therapy for osteoporosis.

Area of Science:

  • Endocrinology
  • Cell Biology
  • Bone Biology

Background:

  • Oestrogen is known to inhibit osteoclastogenesis and activate autophagy.
  • The specific role of oestrogen-regulated autophagy in osteoclast precursors (OCPs) during osteoclastogenesis is not fully understood.

Purpose of the Study:

  • To investigate the effect of 17β-estradiol, the active form of oestrogen, on OCP autophagy and its subsequent impact on osteoclastogenesis.
  • To elucidate the mechanism by which oestrogen influences OCPs and bone metabolism.

Main Methods:

  • OCPs derived from bone marrow-derived macrophages (BMMs) were treated with 17β-estradiol in vitro.
  • Ovariectomy (OVX) mouse models were used for in vivo studies.
  • Autophagic inhibitors and gene silencing were employed to study the role of autophagy in OCP proliferation, differentiation, and bone loss.

Main Results:

  • 17β-estradiol treatment directly enhanced autophagy in OCPs.
  • This enhanced autophagy counteracted the inhibitory effect of 17β-estradiol on RANKL-induced osteoclastogenesis and downstream signaling.
  • Pharmacological or genetic suppression of autophagy amplified the anti-osteoclastogenic and bone-protective effects of 17β-estradiol in OVX mice.

Conclusions:

  • Oestrogen directly promotes OCP autophagy, which appears to inhibit its own anti-osteoclastogenic activity.
  • Targeting autophagy inhibition could potentially enhance the therapeutic efficacy of oestrogen for treating osteoporosis.
Keywords:
LC3RANKLautophagyoestrogenosteoclastogenesis

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