TNF-Alpha and Skeletal Muscle Repair Mechanisms

Details

• Personal Author:
  Hulderman T ; LiJ ; Salmen R ; Simeonova P
• Description:
  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. [Description provided by NIOSH]
• Subjects:
  Genetics Musculoskeletal Diseases Musculoskeletal System Occupational Health Safety
• Keywords:
  Genes In-vitro-studies Injuries Muscle-function Musculoskeletal-system-disorders Skeletal-defects Skeletal-disorders Skeletal-system-disorders
• ISSN:
  0892-6638
• Document Type:
  Text
• Genre:
  Abstract or Summary
• Place as Subject:
  OSHA Region 3 ; West Virginia
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  HELD - Health Effects Laboratory Division
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  18
• Issue:
  4
• NIOSHTIC Number:
  nn:20024708
• Citation:
  FASEB J 2004 Mar; 18(4):A454
• Contact Point Address:
  Toxicology and Molecular Biology Branch, DHSS/CDC/NIOSH, 1095 Willowdale Road, Morgantown, WV 26505
• Federal Fiscal Year:
  2004
• NORA Priority Area:
  Research Tools and Approaches: Exposure Assessment Methods
• Peer Reviewed:
  False
• Source Full Name:
  The FASEB Journal, Experimental Biology 2004, Washington, DC, April 17-21, 2004
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:3bea98a5f1a437b4d9156555183efe1a7b034299659f82ce372c19992ad66c1a28f24164c45feac14037a55aac40f444c2b584511f8099b07b3ddaead0aff007
• Download URL:
  https://stacks.cdc.gov/view/cdc/196364/cdc_196364_DS1.pdf
• File Type:
  [PDF - 521.17 KB ]