Muscle Contractility: The Brotto Research Lab has a beautiful tradition dating back to Dr. Brotto’s mentors (Drs. Thomas Nosek and Robert Godt) in Muscle Contractility studies using ex-vivo models and single muscle fiber preparations. Despite the lab new venues in Analytical Chemistry and Molecular Genetics, these important approaches remain as the core of Physiology in the lab. Drs. Marco and Leticia have trained a handful of new faculty and Research Scientists that are now experts in these important approaches.
Crosstalk Between MLO‐Y4 Osteocytes and C2C12 Muscle Cells Is Mediated by the Wnt/β‐Catenin Pathway
Live Dynamic Imaging: Exciting work in the Brotto by Undergraduate Research Assistant Matthew Fiedler and the Graduate Research Assistant PhD Student from the Varanasi Laboratory Kamal Awad whereas they implemented Live Cell Dynamic Microscopy Imaging to determine muscle cell healing in vitro using the “scratch model.” Instead of the static mode, we now conduct these studies in live, dynamic, continuous recording mode, where we can capture all events.
We also use a number of molecular-genetics, biochemical, bioinformatics, and modeling approaches to our studies. We are a highly collaborative team with collaborators in several US Universities and Centers and in each of Continent of the Globe.
GABA is maninly produced in the Central Nervous System (CNS), spinal cord, and through its central and peripheral action, controls muscle tonicity. Several publications, including our work demonstrate that BAIBA is a myokine secreted from skeletal muscles. It converts white fat into brown fat, and effects the function of osteocytes/bone. We coined the term osteokines for the factors secreted from osteocytes that stimulate the function of muscle cells. Exercise increases the secretion of both myokines and osteokines that can have autocrine and paracrine effects. GABA is a major neurotransmitter with inhibitory functions with very important functions in synaptic transmission, and neuronal development, but it is also essential to relax skeletal muscles; therefore, we proposed a key function of GABA in controlling muscle tonicity. The dotted lines with question marks are hypothetical concepts that muscle tonicity might influence the level of release of myokines, which in turn can influence the levels of BAIBA, while BAIBA might further modulate tonicity. The receptors for GABA and BAIBA mediate their functions and potential SNPs we reported recently in Wang et al., 2020 (Quantification of aminobutyric acids and their clinical applications as biomarkers for osteoporosis) might act as modifiers of these effects. Therefore, we postulate that muscle tonicity could be a new mechanism for the fine-tuning of myokines release and its effects on bone and muscle.