Early Growth Response Genes Increases Rapidly After Mechanical Overloading and Unloading in Tendon Constructs

Area of Science:

• Biomaterials and Tissue Engineering
• Orthopaedic Research
• Cellular and Molecular Biology

Background:

• Tendon strength relies on extracellular matrix development influenced by mechanical loading.
• Understanding tendon cell gene expression under mechanical stress is crucial for tendon repair and regeneration.

Purpose of the Study:

• To analyze temporal gene expression of tendon-related factors during in vitro tendon formation.
• To investigate the sensitivity of early growth response-1 (EGR1), EGR2, FOS, and cyclooxygenase-1 and -2 (PTGS1, PTGS2) to mechanical loading in tendon cells.

Main Methods:

• Utilized a three-dimensional (3D) culture system to mimic in vitro tendon formation.
• Quantified messenger RNA (mRNA) levels of tendon-related genes over time.
• Assessed mRNA expression of specific genes (EGR1, EGR2, FOS, PTGS1, PTGS2) following dynamic physiologic-range loading (2.5% strain), dynamic overloading (~10% strain), and tension release.

Main Results:

• Gene expression for EGR2, MKX, TNMD, and COL3A1 increased over time in the 3D tendon model.
• EGR1, EGR2, FOS, PTGS1, and PTGS2 did not show significant changes with physiologic-range loading.
• Overloading and tension release significantly elevated EGR1 and EGR2 mRNA levels, while FOS and PTGS2 increased with overloading but not tension release.

Conclusions:

• Tendon-related gene expression, including EGR2, naturally increases during in vitro artificial tendon development.
• EGR1 and EGR2 gene expression in human tendon cells are responsive to mechanical overloading and unloading, but not to single episodes of physiologic loading.
• These findings contribute to understanding tendon tensional homeostasis and may inform strategies for tendon injury management.