Macrophages and Skeletal Muscle Regeneration: A Clodronate-Containing Liposome Depletion Study

Details

• Personal Author:
  Chapman R ; Hulderman T ; Mercer RR ; Simeonova PP ; Summan M ; Van Rooijen N ; Warren GL
• Description:
  The study evaluates the influence of monocytes/macrophages in the mechanisms of skeletal muscle injury using a mouse model and selective depletion of peripheral monocyte with systemic injections of liposomal clodronate (dichloromethylene bisphosphonate). This pharmacological treatment has been demonstrated to induce specific apoptotic death in monocytes and phagocytic macrophages. In the current studies, the liposomal clodronate injections resulted in a marked attenuation of the peak inflammatory response in the freeze-injured muscle in the first three days after injury. The effect was accompanied by a transient reduction (at day 1 or 3 postinjury) of the expression of several genes coding for inflammatory, as well as growth-related mediators, including TNF, monocyte chemoattractant protein (MCP)-1, thioredoxin, high-mobility group AT-hook 1, insulin-like growth factor-binding protein (IGFBP), and IGF-1. In contrast, the expression of major myogenic factors (i.e., MyoD and myogenin) directly involved in the activation/proliferation and differentiation of muscle precursor cells was not altered by the clodronate liposome treatment. The repair process in the injured muscle of clodronate liposome-treated mice was characterized by prolonged clearance of necrotic myofibers and a tendency for increased muscle fat accumulation at day 9 and 14 postinjury, respectively. In conclusion, a significant reduction of the initial monocyte/macrophage influx into the injured muscle is associated with not improved, but moderately impaired, repair processes after skeletal muscle injury. [Description provided by NIOSH]
• Subjects:
  Animals Laboratories Musculoskeletal Diseases Musculoskeletal System Occupational Health Safety
• Keywords:
  Animal-studies Injuries Laboratory-animals Models Muscles Physiology Skeletal-disorders Skeletal-system-disorders
• ISSN:
  0363-6119
• Document Type:
  Text
• Genre:
  Journal Article
• 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:
  290
• Issue:
  6
• NIOSHTIC Number:
  nn:20030228
• Citation:
  Am J Physiol Regul Integr Comp Physiol 2006 Jun; 290(6):R1488-1495
• Email:
  PSimeonova@cdc.gov
• Federal Fiscal Year:
  2006
• NORA Priority Area:
  Research Tools and Approaches: Exposure Assessment Methods
• Peer Reviewed:
  True
• Source Full Name:
  American Journal of Physiology: Regulatory, Integrative and Comparative Physiology
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:11211e5d9ddd50a5bd34569406074e622e5f9c6b230f3ab02b1378bed0ec3350381c487b9d6efbcefa4f1554db7bec7242e44bdff60e590a06e8a37ddef06b94
• Download URL:
  https://stacks.cdc.gov/view/cdc/190977/cdc_190977_DS1.pdf
• File Type:
  [PDF - 1.02 MB ]