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High glucose-induced LIF suppresses osteoblast differentiation via regulating STAT3/SOCS3 signaling

Changlu Liu1, Dianming Jiang1

  • 1Department of Orthopaedics, The First Affiliated Hospital of Chongqing Medical University, 400016 Chongqing, China.

Cytokine
|January 9, 2017
PubMed

Insights

High glucose in type 2 diabetes mellitus (T2DM) inhibits osteoblast differentiation by increasing leukemia inhibitory factor (LIF). LIF promotes STAT3/SOCS3 signaling, contributing to bone metabolism disruption in T2DM.

Area of Science:

  • Endocrinology
  • Bone Biology
  • Cell Signaling

Background:

  • High glucose (HG) impacts bone metabolism in diabetic mellitus (DM).
  • Leukemia inhibitory factor (LIF), an IL-6 family cytokine, plays a role in cellular regulation.
  • Understanding HG's effect on bone in T2DM is crucial for metabolic bone disease research.

Purpose of the Study:

  • To investigate LIF levels in T2DM patients.
  • To explore HG's regulation of LIF/STAT3 signaling.
  • To determine the impact of HG and LIF on osteoblast differentiation and the role of SOCS3/STAT3 signaling.

Main Methods:

  • Measured serum markers (hsCRP, IL-1β, IL-6, LIF) in T2DM patients.
  • In vitro study using human osteoblast MG-63 cells exposed to HG.
  • Assessed osteogenic markers (ALP, OCN, RUNX2, OPN) at mRNA and protein levels.
  • Investigated STAT3 phosphorylation and SOCS3 expression, using STAT3 inhibitor JSI-124.

Main Results:

  • T2DM patients exhibited elevated hsCRP, IL-1β, IL-6, and LIF.
  • HG increased these cytokine levels in vitro.
  • Both HG and LIF reduced osteogenic marker expression (ALP, OCN, RUNX2).
  • LIF promoted SOCS3 expression and STAT3 phosphorylation; STAT3 inhibition restored osteogenic markers.

Conclusions:

  • LIF is involved in HG-induced inhibition of osteoblast differentiation.
  • The mechanism involves the promotion of STAT3/SOCS3 signaling by LIF.
  • Findings offer insights into HG-induced bone loss and impaired healing in T2DM.
Keywords:
High glucoseLIFOsteoblast differentiationSTAT3/SOCS3 signaling

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