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  5. Predictive And Prognostic Markers
  6. Loss Of Periostin Function Impairs Ligament Fibroblast Activity And Facilitates Ros-mediated Cellular Senescence

Loss of periostin function impairs ligament fibroblast activity and facilitates ROS-mediated cellular senescence

Muhammad Farooq Rai1,2,3,4, Xin Duan5,6, Mingming Yan5,7

  • 1Department of Biological Sciences, College of Medicine and Health Sciences, Khalifa University, Abu Dhabi, United Arab Emirates.

FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology
|August 20, 2024

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View abstract on PubMed

Summary
This summary is machine-generated.

Periostin is crucial for anterior cruciate ligament (ACL) health and healing. Its deficiency impairs fibroblast function, promotes cell death and senescence, and increases ACL tear susceptibility, highlighting its role in ligament repair.

Area of Science:

  • Orthopedics
  • Biomedical Engineering
  • Cell Biology

Background:

  • Anterior cruciate ligament (ACL) injuries have poor healing potential, leading to arthritis.
  • Factors influencing ACL's inadequate healing are not fully understood.
  • Periostin levels are elevated in acute ACL injuries but decrease over time.

Purpose of the Study:

  • Investigate the functional and mechanistic roles of periostin in ACL biology.
  • Determine the impact of periostin deficiency on ligament fibroblast behavior and ACL integrity.

Main Methods:

  • Utilized patient-derived ligament fibroblasts and a murine model of ACL rupture.
  • Performed periostin knockdown experiments.
  • Analyzed cell-cycle progression, apoptosis, senescence, gene expression, and reactive oxygen species (ROS) production.
Keywords:
ACLROSSTAT3cell‐cycle

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  • Assessed ACL tearing frequency in periostin-deficient (Postn-/-) mice.
  • Main Results:

    • Periostin deficiency impaired fibroblast growth, progenitor cell egress, and cell-cycle progression (G0/G1 arrest).
    • Reduced expression of cell-cycle and matrix genes observed.
    • Periostin deficiency induced apoptosis via STAT3/p38 MAPK signaling and senescence via ROS production.
    • Postn-/- mice showed increased ACL tearing frequency.
    • Silenced periostin in injured ACL increased apoptosis and senescence.

    Conclusions:

    • Periostin plays a critical role in maintaining ACL health and promoting healing.
    • Periostin deficiency compromises ligament fibroblast function, leading to increased cell death and senescence.
    • Periostin is essential for ACL's mechanical integrity and resistance to injury.
    p16INK4A
    p38MAPK