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Isolation and Quantitative Immunocytochemical Characterization of Primary Myogenic Cells and Fibroblasts from Human Skeletal Muscle
11:22

Isolation and Quantitative Immunocytochemical Characterization of Primary Myogenic Cells and Fibroblasts from Human Skeletal Muscle

Published on: January 12, 2015

ADAM12 and alpha9beta1 integrin are instrumental in human myogenic cell differentiation

Peggy Lafuste1, Corinne Sonnet, Bénédicte Chazaud

  • 1Institut National de la Santé et de la Recherche Médicale EMI 0011, Faculty of Medicine, Paris XII University, Creteil 94010, France.

Molecular Biology of the Cell
|December 3, 2004
PubMed

Insights

The interaction between ADAM12 and alpha9beta1 integrin is crucial for human muscle precursor cell fusion. Inhibiting this pathway significantly reduces myotube formation, particularly for larger myotubes.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Myogenic precursor cell (MPC) fusion into myotubes is essential for muscle development but incompletely understood.
  • The ADAM (a disintegrin and metalloproteinase) family is implicated in mammalian cell fusion.
  • ADAM12 has been suggested to play a role in MPC fusion, potentially requiring interaction with other molecules like alpha9beta1 integrin.

Purpose of the Study:

  • To investigate the role of ADAM12 and alpha9beta1 integrin in human MPC fusion.
  • To determine if ADAM12 and alpha9beta1 integrin interact and contribute to MPC adhesion and fusion.
  • To assess the impact of inhibiting the ADAM12-alpha9beta1 integrin interaction on myotube formation.

Main Methods:

  • Quantifying ADAM12 and alpha9beta1 integrin expression during human MPC differentiation.
  • Performing co-immunoprecipitation to assess ADAM12 and alpha9beta1 integrin interaction.
  • Using ADAM12 antisense oligonucleotides and anti-alpha9beta1 blocking antibodies to inhibit their interaction.
  • Measuring MPC fusion rates and myotube size distribution.

Main Results:

  • ADAM12 and alpha9beta1 integrin are co-expressed and co-immunoprecipitate during human MPC differentiation and fusion.
  • Inhibition of ADAM12 or alpha9beta1 integrin significantly reduced MPC fusion (47-48%), with combined inhibition reaching 62%.
  • The ADAM12-alpha9beta1 blockade specifically impacted fusion, not cell adhesion to the extracellular matrix, and preferentially inhibited the formation of large myotubes.

Conclusions:

  • ADAM12 and alpha9beta1 integrin are key molecular players in postnatal human myogenic differentiation.
  • Their interaction is essential for efficient MPC fusion and particularly important for the growth of nascent myotubes.
  • Targeting the ADAM12-alpha9beta1 integrin pathway offers a specific approach to modulate myotube formation.

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