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CTLA4-Ig sustains osteogenic potential and inhibits osteoclastogenesis in Staphylococcus aureus osteomyelitis

Rongjie Lin1, Yiqing Huang1, Zhenbin Chen1

  • 1Department of Orthopedic Surgery, Fujian Medical University Union Hospital, Fuzhou, 350001, China.

Bone
|November 18, 2025
PubMed

Insights

Cytotoxic T-lymphocyte-associated protein 4 (CTLA4)-Ig shows promise for treating osteomyelitis (OM). It promotes bone regeneration and reduces bone destruction by modulating the immune microenvironment, offering a dual therapeutic approach.

Area of Science:

  • Immunology
  • Orthopedics
  • Regenerative Medicine

Background:

  • Osteomyelitis (OM) is a severe bone disease involving infection and inflammation.
  • Identifying key regulators for immune modulation and bone regeneration is crucial for OM treatment.

Purpose of the Study:

  • To investigate the role of CTLA4 in osteomyelitis.
  • To evaluate the therapeutic potential of CTLA4-Ig in promoting bone regeneration and inhibiting bone destruction in OM.

Main Methods:

  • Transcriptomic analysis of OM datasets (GSE18043, GSE30119).
  • Bioinformatic and immune infiltration analyses.
  • In vitro studies using MC3T3-E1 cells.
  • In vivo studies using a Staphylococcus aureus-induced rat OM model.

Main Results:

  • CTLA4 expression correlated with anti-inflammatory macrophage infiltration and Wnt/β-catenin pathway activation.
  • CTLA4-Ig promoted osteogenic differentiation and matrix mineralization in vitro.
  • CTLA4-Ig inhibited osteoclast formation and bone resorption in vitro.
  • CTLA4-Ig treatment in vivo enhanced osteoblast activity, reduced osteoclast presence, and improved bone structural integrity.
  • CTLA4-Ig modulated the inflammatory microenvironment, reducing pro-inflammatory cytokines and bacterial burden.

Conclusions:

  • CTLA4 is a key regulator in osteomyelitis, influencing immune modulation and osteogenic differentiation.
  • CTLA4-Ig demonstrates dual action, promoting bone regeneration while inhibiting bone destruction.
  • CTLA4-Ig represents a promising therapeutic strategy for osteomyelitis by modulating the inflammatory microenvironment and enhancing bone repair.
Keywords:
CTLA4Osteogenic differentiationOsteomyelitisStaphylococcus aureusWnt/β-catenin

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