Role of TNF Alpha and PLF in Bone Remodeling in a Rat Model of Repetitive Reaching and Grasping

Details

• Personal Author:
  Barbe MF ; Barr AE ; Litvin J ; Rani S
• Description:
  We have previously developed a voluntary rat model of highly repetitive reaching that provides an opportunity to study effects of non-weight bearing muscular loads on bone and mechanisms of naturally occurring inflammation on upper limb tissues in vivo. In this study, we investigated the relationship between inflammatory cytokines and matricellular proteins (Periostin-like-factor, PLF, and connective tissue growth factor, CTGF) using our model. We also examined the relationship between inflammatory cytokines, PLF and bone formation processes. Rats underwent initial training for 5 weeks, and then performed a high repetition high force (HRHF) task (12 reaches/min, 60% maximum grip force, 2 h/day, 3 days/week) for 6 weeks. We then examined the effect of training or task performance with or without treatment with a rat specific TNFa antibody on inflammatory cytokines, osteocalcin (a bone formation marker), PLF, CTGF, and behavioral indicators of pain or discomfort. The HRHF task decreased grip strength and induced forepaw mechanical hypersensitivity in both trained control and 6-week HRHF animals. Two weeks of anti-TNFa treatment improved grip strength in both groups, but did not ameliorate forepaw hypersensitivity. Moreover, anti-TNFa treatment attenuated task-induced increases in inflammatory cytokines (TNFa, IL-1a, and MIP2 in serum; TNFa in forelimb bone and muscles) and serum osteocalcin in 6-week HRHF animals. PLF levels in forelimb bones and flexor digitorum muscles increased significantly in 6-week HRHF animals, increases attenuated by anti-TNFa treatment. CTGF levels were unaffected by task performance or anti-TNFa treatment in 6-week HRHF muscles. In primary osteoblast cultures, TNFa, MIP2 and MIP3a treatment increased PLF levels in a dose dependent manner. Also in primary osteoblast cultures, increased PLF promoted proliferation and differentiation, the latter assessed by measuring Runx2, alkaline phosphatase (ALP) and osteocalcin mRNA levels; ALP activity; as well as calcium deposition and mineralization. Increased PLF also promoted cell adhesion in MC3T3-E1 osteoblast-like cell cultures. Thus, tissue loading in vivo resulted in increased TNFa, which increased PLF, which then induced anabolic bone formation, the latter results confirmed in vitro. [Description provided by NIOSH]
• Subjects:
  Immune System Occupational Health Safety
• Keywords:
  Bone Structure Cellular Effects Cytokines Immune Reaction Immunology Repetitive Work
• ISSN:
  0021-9541
• Document Type:
  Text
• Funding:
  Grant
• Genre:
  Journal Article
• Place as Subject:
  OSHA Region 3 ; Pennsylvania
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Pages in Document:
  152-167
• Volume:
  225
• Issue:
  1
• NIOSHTIC Number:
  nn:20056291
• Citation:
  J Cell Physiol 2010 Oct; 225(1):152-167
• Contact Point Address:
  Judith Litivn, Department of Anatomy and Cell Biology, Temple Medical School, Philadelphia, PA 19140
• Email:
  judith.litvin@temple.edu
• Federal Fiscal Year:
  2011
• Performing Organization:
  Temple University
• Peer Reviewed:
  True
• Start Date:
  20000601
• Source Full Name:
  Journal of Cellular Physiology
• End Date:
  20120731
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:d8aaf8ba27dbbb5301b17e4304fdc73dc767ce2199061b6cc6fc88c67d8fcc2c44272eb2d585c9932941d9bdd4f006ae4a56278639c342e8a9edef6309352fd0
• Download URL:
  https://stacks.cdc.gov/view/cdc/213927/cdc_213927_DS1.pdf
• File Type:
  [PDF - 711.79 KB ]