Matrix stiffness regulates Mkx expression in rat tenocyte through TRPM7

Area of Science:

• Biotechnology
• Biomaterials Science
• Cell Biology

Background:

• Tendon cells are exposed to mechanical stimuli, including tensile force and shear stress.
• The response of tenocytes (tendon cells) to matrix stiffness, a critical mechanical cue, was previously unclear.
• Mesenchymal stem cells and tendon-derived stem cells show stiffness-dependent tenogenic gene expression, but the effect on fibroblasts was unknown.

Purpose of the Study:

• To investigate the role of matrix stiffness in regulating tenocytes.
• To identify molecular mechanisms underlying stiffness-dependent gene expression in tenocytes.
• To explore the role of the TRPM7 channel in tendon cell mechanotransduction.

Main Methods:

• Culturing tenocytes derived from rat tail and Achilles tendons on varying stiffness substrates.
• Analyzing the expression of tendon-related genes, including Mkx, using quantitative methods.
• Investigating the function of the TRPM7 channel through knockdown experiments and ion manipulation.

Main Results:

• Tenocytes exhibited stiffness-dependent gene expression, notably for Mkx at 40 kPa.
• The transient receptor potential melastatin 7 (TRPM7) channel was identified as a key regulator of stiffness-dependent Mkx expression.
• TRPM7 knockdown abolished stiffness-dependent Mkx expression, suggesting regulation via Ca2+ and/or Mg2+ ion influx.

Conclusions:

• Matrix stiffness significantly influences tenocyte gene expression, particularly Mkx.
• The TRPM7 channel plays a crucial role in mediating the effects of matrix stiffness on tenocytes.
• This study provides new insights into tendon mechanotransduction and the regulation of Mkx expression.