Nobiletin ameliorates hormone-induced osteoblast apoptosis by modulating JAK2/STAT3 signaling

Xiang Li1, Yuanzhen Bai1, Jia Tong2

  • 1Nanjing University of Chinese Medicine, 210023, Nanjing, China.

PubMed

Insights

Nobiletin (NOB) protects against hormone-induced osteoblast apoptosis by inhibiting the JAK2/STAT3 pathway. This natural compound enhances cell viability and reduces inflammatory markers, offering a potential therapeutic strategy for bone health.

Area of Science:

  • Biochemistry
  • Cell Biology
  • Pharmacology

Background:

  • Hormone-induced osteoblast apoptosis contributes to bone diseases.
  • Glucocorticoids (GC) are known to induce osteoblast apoptosis.
  • Nobiletin (NOB) is a flavonoid with potential therapeutic properties.

Purpose of the Study:

  • To investigate the effects of nobiletin (NOB) on hormone-induced osteoblast apoptosis.
  • To elucidate the underlying mechanism of NOB's action, particularly its effect on the JAK2/STAT3 pathway.

Main Methods:

  • MC3T3-E1 osteoblast cell line was used.
  • Cells were treated with glucocorticoid (GC) and varying concentrations of NOB.
  • Cell viability (CCK-8), apoptosis (FITC-Annexin V/PI), ALP activity, inflammatory cytokine levels (IL-6, IL-1β, TNF-α), ROS levels, and JAK2/STAT3 pathway protein expression (Western blotting) were assessed.

Main Results:

  • GC treatment increased osteoblast apoptosis, reduced cell viability and ALP activity, and elevated inflammatory markers (IL-6, IL-1β, TNF-α, ROS) and apoptosis-related proteins (Caspase-3, Bax).
  • NOB treatment dose-dependently reversed these effects, increasing cell viability, ALP activity, and Bcl-2 levels, while decreasing apoptosis, inflammation, ROS, and downstream JAK2/STAT3 signaling.
  • Activation of JAK2/STAT3 signaling with Colivelin counteracted NOB's protective effects.

Conclusions:

  • Nobiletin (NOB) effectively ameliorates hormone-induced osteoblast apoptosis.
  • NOB exerts its protective effects by inhibiting the JAK2/STAT3 signaling pathway.
  • NOB demonstrates potential as a therapeutic agent for conditions involving osteoblast apoptosis.

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