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ULK1 Suppresses Osteoclast Differentiation and Bone Resorption via Inhibiting Syk-JNK through DOK3

Yufeng Zhang1, Sheng Zhang1, Yi Wang1

  • 1Department of Spine Surgery and Musculoskeletal Tumor, Department of Orthopedics, Zhongnan Hospital of Wuhan University, Wuhan 430071, China.

Oxidative Medicine and Cellular Longevity
|November 25, 2021
PubMed

Insights

Unc-51-like autophagy activating kinase 1 (ULK1) inhibits osteoclast formation, a key factor in osteoporosis. Targeting ULK1 shows promise as a new therapeutic strategy for bone resorption diseases.

Area of Science:

  • Biochemistry
  • Cell Biology
  • Orthopedics

Background:

  • Osteoporosis and other bone resorption diseases stem from excessive osteoclastogenesis.
  • Unc-51-like autophagy activating kinase 1 (ULK1) is implicated in bone homeostasis and osteolytic metastasis.

Purpose of the Study:

  • To investigate the role of ULK1 in osteoclastogenesis and bone resorption.
  • To explore ULK1 as a potential therapeutic target for osteoporosis.

Main Methods:

  • Detected ULK1 expression using RT-PCR in bone marrow macrophages (BMM).
  • Manipulated ULK1 levels via siRNA and lentiviral transduction.
  • Assessed osteoclastogenesis using TRAP and phalloidin staining.
  • Utilized ovariectomized (OVX) mouse models for in vivo studies.

Main Results:

  • ULK1 expression decreased during osteoclast differentiation and correlated with osteoporosis.
  • ULK1 inhibited osteoclast differentiation and bone resorption in vitro and in vivo.
  • ULK1 knockdown increased JNK and Syk phosphorylation; DOK3 coexpression modulated this effect.
  • ULK1 activation protected against bone loss in OVX mice.

Conclusions:

  • A novel ULK1/DOK3/Syk signaling axis regulates osteoclast differentiation and bone resorption.
  • ULK1 activation represents a potential therapeutic strategy for osteoporosis and related bone diseases.

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