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Updated: Jan 10, 2026

Skeletal Phenotype Analysis of a Conditional Stat3 Deletion Mouse Model
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Skeletal Phenotype Analysis of a Conditional Stat3 Deletion Mouse Model

Published on: July 3, 2020

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Mycl, activated by Sgk1-phosphorylated Stat3, mediates osteoclastogenesis via Ctsk transcriptional regulation

Yiru Wang1, Chensong Yang2, Fuming Cao3

  • 1Department of VIP Clinic, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, 200025, China.

Scientific Reports
|November 20, 2025
PubMed

Insights

Serum/glucocorticoid-regulated kinase 1 (Sgk1) is a key regulator of osteoclast differentiation. Inhibiting Sgk1 enhances bone mass and strength, suggesting Sgk1 inhibition as a potential osteoporosis therapy.

Area of Science:

  • Molecular Biology
  • Bone Biology
  • Endocrinology

Background:

  • Osteoclast differentiation is crucial for bone homeostasis but its regulation is not fully understood.
  • Hormonal signals influence bone metabolism through various kinases.
  • Identifying novel regulators of osteoclastogenesis is vital for developing osteoporosis treatments.

Purpose of the Study:

  • To identify novel molecular regulators of osteoclastogenesis.
  • To investigate the role of serum/glucocorticoid-regulated kinase 1 (Sgk1) in osteoclast differentiation.
  • To explore the therapeutic potential of Sgk1 inhibition in bone diseases.

Main Methods:

  • Investigated the role of Sgk1 in osteoclast differentiation using molecular and cellular assays.
  • Analyzed Stat3 phosphorylation, Mycl expression, and Ctsk promoter binding.
  • Utilized in vivo studies with an Sgk1 inhibitor (GSK650394) to assess effects on bone mass and strength.

Main Results:

  • Sgk1 was identified as a key regulator of osteoclastogenesis.
  • Sgk1 inhibition reduced Stat3 phosphorylation and Mycl expression, impacting osteoclast differentiation.
  • Mycl was found to directly bind the Ctsk promoter, playing a critical role in the process.
  • In vivo Sgk1 inhibition increased trabecular bone mass and mechanical strength without affecting osteoblasts.

Conclusions:

  • A novel Sgk1-Stat3-Mycl-Ctsk signaling axis regulating osteoclastogenesis was defined.
  • Sgk1 inhibition represents a promising therapeutic strategy for osteoporosis.
  • Targeting Sgk1 offers a potential approach to enhance bone health and combat bone loss.
Keywords:
Bone remodelingMyclOsteoclastogenesisSgk1Stat3 signaling

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