Effect of mechanical stimulation on tissue heterotopic ossification: an in vivo experimental study

Frontiers in Physiology, 2023 · DOI: 10.3389/fphys.2023.1225898 · Published: October 11, 2023

Simple Explanation

This study investigates how mechanical forces affect heterotopic ossification (HO), a condition where bone forms in tendons and ligaments. The researchers used mice with a genetic mutation that causes HO to study the effects of spinal immobilization and treadmill exercise on the development of HO in the spine and Achilles tendons. The mice were divided into three groups: a control group, a group that had their spines immobilized with a brace, and a group that underwent treadmill training. The degree of ossification in the spinal ligament and Achilles tendon was evaluated using micro-CT scanning and HE staining. The study found that spinal immobilization delayed spinal ligament ossification, while treadmill training enhanced it. Furthermore, they found that the protein YAP, which is involved in the response to mechanical stimulation, was more highly expressed in tissues with severe ossification.

Study Duration
28 Weeks
Participants
Enpp1 gene deficiency mice
Evidence Level
Level 3, Animal Experimental Study

Key Findings

  • 1
    Spinal immobilization effectively restricts the flexion and extension of cervical and thoracic vertebrae in mice, delaying spinal ligament ossification and reducing chronic secondary spinal cord injury.
  • 2
    Running exercises not only enhance the ossification area of the posterior longitudinal ligament (PLL) and Achilles tendons but also exacerbate secondary spinal cord injury.
  • 3
    YAP expression levels were notably increased in tissues with severe ossification, suggesting that these tissues may be subjected to higher mechanical stimulation.

Research Summary

This study investigates the role of mechanical stimulation in heterotopic ossification (HOTL) using a mouse model with Enpp1 gene deficiency. The mice were subjected to spinal immobilization and treadmill training to observe the effects on ossification. The results showed that spinal immobilization delayed spinal ligament ossification, while treadmill training exacerbated it and secondary spinal cord injury. Immunofluorescence revealed increased YAP expression in tissues with severe ossification. The study concludes that mechanical stimulation plays a pivotal role in HOTL and provides valid animal models for further exploration of pathological mechanisms.

Practical Implications

Animal Model Development

The study provides a novel animal model to further explore the pathological mechanism of mechanical stimulation in HOTL development.

Therapeutic Strategies

The study suggests that limiting spinal movement may be a therapeutic strategy to delay the progression of heterotopic ossification.

Rehabilitation Considerations

The study raises concerns about the benefits of running exercise for neurological function recovery in OPLL patients, suggesting that it may exacerbate spinal cord injury.

Study Limitations

  • 1
    The external fixation brace was less effective than internal fixation due to soft tissue cushioning.
  • 2
    The accuracy of HE staining of axial sections was limited by frozen section technology.
  • 3
    The genetically defective mice used in this study develop ossification of ligament tissue throughout the whole body.

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