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TNF-α suppresses osteogenic differentiation of MSCs by accelerating P2Y2 receptor in estrogen-deficiency induced

Di Du1, Zhibin Zhou1, Lei Zhu1

  • 1Department of Orthopedics and Trauma Surgery, Changzheng Hospital, the Second Military Medical University, Shanghai, China.

Bone
|September 22, 2018
PubMed

Insights

Tumor Necrosis Factor-α (TNF-α) impairs bone formation by affecting mesenchymal stem cells (MSCs). This study reveals the P2Y2 receptor is key in this process, offering a new target for osteoporosis treatment.

Area of Science:

  • Cell Biology
  • Biochemistry
  • Orthopedics

Background:

  • Tumor Necrosis Factor-α (TNF-α) inhibits osteogenic differentiation of mesenchymal stem cells (MSCs), contributing to postmenopausal osteoporosis.
  • The precise mechanisms underlying TNF-α-induced inhibition of osteoblast differentiation remain unclear.
  • P2 purinoceptors are known regulators of bone metabolism in osteoblasts.

Purpose of the Study:

  • To investigate the role of P2 purinoceptors in TNF-α-inhibited osteoblast differentiation.
  • To determine if P2Y2 receptor is involved in TNF-α's effects on MSCs.

Main Methods:

  • Examined P2Y2 receptor expression during MSC osteogenic differentiation under TNF-α influence.
  • Utilized gene overexpression and silencing techniques for P2Y2 receptor.
  • Investigated the involvement of ERK and JNK signaling pathways.

Main Results:

  • TNF-α significantly increased P2Y2 receptor expression during MSC osteogenic differentiation.
  • Modulating P2Y2 receptor expression (overexpression or silencing) altered MSC osteogenic differentiation.
  • Silencing P2Y2 receptor counteracted TNF-α's inhibitory effects on osteoblast differentiation and MSC proliferation.
  • TNF-α upregulated P2Y2 receptor expression via ERK and JNK signaling pathways.

Conclusions:

  • P2Y2 receptor plays a critical role in TNF-α-inhibited osteogenic differentiation of MSCs.
  • Targeting P2Y2 receptor may offer a therapeutic strategy for osteoporosis, particularly in estrogen deficiency-induced cases.
Keywords:
Osteoblast differentiationP2Y(2) receptorPostmenopausal osteoporosisTNF-α

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