Faculty Advisor

Jonathan W. Lowery, Ph.D.

Document Type


Publication Date



Medicine and Health Sciences


The Activin and BMP signaling pathways exert reciprocal effects on myogenesis and skeletal muscle regeneration after injury. Signal transduction in both pathways is mediated by ligand- induced activation of transcriptional regulators called SMAD proteins, with Activins leading to phosphorylation of SMAD2/3 and BMPs leading to phosphorylation of SMAD1/5/8. These ligands bind to their own type I receptors but can also compete for shared type II receptors (ACVR2A and/or ACVR2B). However, it is unclear how these pathways interact in skeletal muscle progenitor cells. To address this deficiency, we investigated the effects of the ligands BMP2 and Activin-A on C2C12 cells, which are an immortalized mouse myoblast cell line with myogenic potential, using a sequence of pre-treatment and co-treatment assays followed by western blot analyses to examine the activation level of their respective SMAD proteins. As expected, treatment with exogenous BMP2 or Activin A led to phosphorylation of SMAD1/5/8 and SMAD2/3, respectively. Moreover, pre-treatment of C2C12 cells with Activin-A before BMP2 delivery resulted in an attenuated phosphorylation of SMAD1/5/8; this effect seems to be specific to Activin ligands, though, since the converse relationship was not observed with respect to phosphorylation of SMAD2/3. Interestingly, seemingly contradictory results were observed when Activin-A and BMP2 were delivered to C2C12 cells simultaneously; this co-treatment scenario results in a higher level of SMAD1/5/8 phosphorylation than delivery of either ligand alone. Ongoing experiments seek to elucidate the mechanism(s) impacting the cellular responses under sequential versus simultaneous activation by Activin and BMP ligands. A better understanding of these mechanisms could lead to novel therapeutic strategies for regeneration of skeletal muscle tissue after injury.


Copyright 2017 all authors


Division of Biomedical Science, Marian University College of Osteopathic Medicine, Indianapolis, IN, USA