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TNF-alpha and skeletal muscle repair mechanisms.
Hulderman-T; Salmen-R; Li-J; Simeonova-P
FASEB J 2004 Mar; 18(4):A454
We have demonstrated that TNFa is activated in injured skeletal muscle and attenuation of its signaling leads to delay in muscle functional recovery post-injury. In vitro TNFa induces proliferation and migration but suppresses differentiation of myoblasts. The responses attributed to TNFa are not a direct result of TNFa, but rather its ability to regulate the expression of TNFa responsive genes whose products directly mediate the response. TNFa delivers its signals to target cells by binding to specific cell surface membrane receptors (TNFR1 and TNFR2). DNA array or real-time PCR techniques were used to evaluate gene expression induced by TNFa in myoblast cultures. TNFa induces high expression of chemokines, (e.g. MCP-1) and adhesion molecules (VCAM-1), in proliferating or differentiating C2C12 cells and primary myoblasts. This response may be related to myoblast migration or fusion activities. Furthermore, TNFa induces moderate induction of Pax-7, a mediator of myoblast proliferation. For TNFa induced inhibition of myoblast differentiation myogenin expression was reduced. Myoblasts from TNFR1 and TNFR2 deficient mice demonstrated that TNFa induced gene expression in primary myoblasts is dependent on both receptors. These studies indicate that a complex and multifunctional role exists for inflammation, and specifically TNFa, in post-traumatic skeletal muscle regeneration and healing.
Skeletal-system-disorders; Skeletal-disorders; Skeletal-defects; Musculoskeletal-system-disorders; Injuries; Muscle-function; In-vitro-studies; Genes
Toxicology and Molecular Biology Branch, DHSS/CDC/NIOSH, 1095 Willowdale Road, Morgantown, WV 26505
Issue of Publication
Research Tools and Approaches: Exposure Assessment Methods
The FASEB Journal, Experimental Biology 2004, Washington, DC, April 17-21, 2004
Page last reviewed: March 11, 2019
Content source: National Institute for Occupational Safety and Health Education and Information Division