Pb inhibited C2C12 myoblast differentiation by regulating HDAC2.

Area of Science:

• Cell Biology
• Toxicology
• Developmental Biology

Background:

• Myogenesis is vital for skeletal muscle development and homeostasis.
• Lead (Pb) exposure negatively impacts bone health, particularly in children.
• The specific effects of lead on skeletal muscle development remain largely unknown.

Purpose of the Study:

• To investigate the toxic effects of lead (Pb) on C2C12 myoblast proliferation and differentiation.
• To elucidate the role of histone deacetylase-2 (HDAC2) in Pb-induced inhibition of myogenesis.

Main Methods:

• C2C12 myoblasts were exposed to varying concentrations of Pb (1, 5, and 10 μM).
• Cell viability assays were performed to assess Pb toxicity.
• Myogenic differentiation markers (MCK, MYH4, MYOG, MYOD) and HDAC2 expression were analyzed.
• HDAC2 knockdown was employed to determine its role in Pb-induced differentiation deficits.

Main Results:

• Pb exposure at 5 μM and 10 μM significantly decreased C2C12 cell viability.
• Pb exposure (1-10 μM) markedly inhibited myoblast differentiation, reducing key myogenic marker gene expression.
• Lead exposure led to the upregulation of histone deacetylase-2 (HDAC2) in C2C12 myoblasts.
• Knockdown of HDAC2 partially rescued the Pb-induced inhibition of C2C12 myoblast differentiation.

Conclusions:

• Lead exposure inhibits skeletal muscle development by impairing C2C12 myoblast differentiation.
• The epigenetic modifier histone deacetylase-2 (HDAC2) plays a critical role in mediating Pb-induced myogenesis deficits.
• These findings reveal a novel mechanism of lead toxicity impacting skeletal muscle development.