Pro-Inflammatory Mediation of Myoblast Proliferation

Abstract

Skeletal muscle satellite cell function is largely dictated by the surrounding environment following injury. Immune cell infiltration dominates the extracellular space in the injured area, resulting in increased cytokine concentrations. While increased pro-inflammatory cytokine expression has been previously established in the first 3 days following injury, less is known about the time course of cytokine expression and the specific mechanisms of cytokine induced myoblast function. Therefore, the expression of IL-1β and IL-6 at several time points following injury, and their effects on myoblast proliferation, were examined. In order to do this, skeletal muscle was injured using barium chloride in mice and tissue was collected 1, 5, 10, and 28 days following injury. Mechanisms of cytokine induced proliferation were determined in cell culture using both primary and C2C12 myoblasts. It was found that there is a ∼20-fold increase in IL-1β (p≤0.05) and IL-6 (p = 0.06) expression 5 days following injury. IL-1β increased proliferation of both primary and C2C12 cells ∼25%. IL-1β stimulation also resulted in increased NF-κB activity, likely contributing to the increased proliferation. These data demonstrate for the first time that IL-1β alone can increase the mitogenic activity of primary skeletal muscle satellite cells and offer insight into the mechanisms dictating satellite cell function following injury.

Inflammatory response during slow- and fast-twitch muscle regeneration

“…As leukocytes, macrophages, and neutrophils secrete pro‐ and anti‐inflammatory factors that are crucial for proper muscle regeneration, they prepare the muscle for rebuilding. Next, they not only remove necrotic fibers but also promote removal of damaged blood vessels …”

“…Thus, a different profile of IL‐6 observed during regeneration of EDL and soleus muscles may cause the observed differences in neutrophil number and may trigger fiber atrophy and affect muscle repair. Besides IL‐6, leukemia inhibitory factor and IFN‐γ were also shown to increase cell division of embryonic myoblasts as well as C2C12 myoblasts …”

Developing a pro-regenerative biomaterial scaffold microenvironment requires T helper 2 cells

“…Conversely, the immune system is a highly flexible network that serves as a guardian of tissue integrity and is adapted to the nature of the local microenvironment (2). The immune system participates in tissue repair by scavenging debris and dead cells (3), recruiting and supporting the proliferation of tissue progenitor cells (4), and inducing vascularization (5). Previously, immune responses to biomaterials were related to rejection (6–8); however, subsets of innate immune cells have been identified as important mediators of scaffold remodeling (9–11) and can be targeted for immune-mediated tissue regeneration.…”

Ascorbic acid diminishes bone morphogenetic protein 2‐induced osteogenic differentiation of muscle precursor cells

“…After 24 h, fixed cells were transferred to precoated 15‐ml tubes (precoated with 1% BSA/DPBS solution for approximately 20 min) and centrifuged at 200 g for 15 minutes at RT. The number of BrdU‐positive cells was then determined as previously described …”