Toll-Like Receptor 4 Signaling Pathway Mediates Inhalant Organic Dust-Induced Bone Loss

Details

• Personal Author:
  Clarey D ; Duryee MJ ; Dusad A ; Klassen LW ; Mikuls TR ; Poole JA ; Romberger DJ ; Staab E ; Thiele GM ; Wang D ; Wells AD ; Wyatt TA
• Description:
  Agriculture workers have increased rates of airway and skeletal disease. Inhalant exposure to agricultural organic dust extract (ODE) induces bone deterioration in mice; yet, mechanisms underlying lung-bone crosstalk remain unclear. Because Toll-like receptor 2 (TLR2) and TLR4 are important in mediating the airway consequences of ODE, this study investigated their role in regulating bone responses. First, swine facility ODE stimulated wild-type (WT) bone marrow macrophages to form osteoclasts, and this finding was inhibited in TLR4 knock-out (KO), but not TLR2 KO cells. Next, using an established intranasal inhalation exposure model, WT, TLR2 KO and TLR4 KO mice were treated daily with ODE or saline for 3 weeks. ODE-induced airway neutrophil influx and cytokine/chemokine release were similarly reduced in TLR2 and TLR4 KO animals as compared to WT mice. Utilizing micro-computed tomography (CT), analysis of tibia showed loss of bone mineral density, volume and deterioration of bone micro-architecture and mechanical strength induced by ODE in WT mice were significantly reduced in TLR4 but not TLR2 KO animals. Bone marrow osteoclast precursor cell populations were analyzed by flow cytometry from exposed animals. In WT animals, exposure to inhalant ODE increased osteoclast precursor cell populations as compared to saline, an effect that was reduced in TLR4 but not TLR2 KO mice. These results show that TLR2 and TLR4 pathways mediate ODE-induced airway inflammation, but bone deterioration consequences following inhalant ODE treatment is strongly dependent upon TLR4. Thus, the TLR4 signaling pathway appears critical in regulating the lung-bone inflammatory axis to microbial component-enriched organic dust exposures. [Description provided by NIOSH]
• Subjects:
  Animals Dust Farmers Lung Diseases Occupational Health Respiratory System Respiratory Tract Diseases Safety
• Keywords:
  Animal Studies Bone Disorders Cytokines Dust Exposure Farm Workers Lung Disease Organic Dusts Physiological Effects Physiological Response Respirable Dust Respiratory Diseases

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• ISSN:
  1932-6203
• Document Type:
  Text
• Funding:
  Grant ; Cooperative Agreement
• Genre:
  Journal Article
• Place as Subject:
  Nebraska ; OSHA Region 7
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  11
• Issue:
  8
• NIOSHTIC Number:
  nn:20053146
• Citation:
  PLoS One 2016 Aug; 11(8):e0158735
• Contact Point Address:
  Jill A. Poole, Pulmonary, Critical Care, Sleep & Allergy Division, Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE, United States of America
• Email:
  japoole@unmc.edu
• Federal Fiscal Year:
  2016
• NORA Priority Area:
  Agriculture, Forestry and Fishing
• Performing Organization:
  University of Nebraska Medical Center, Omaha, Nebraska
• Peer Reviewed:
  True
• Start Date:
  20060801
• Source Full Name:
  PLoS One
• End Date:
  20160731
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:27b1ee5c30b4776d7f5b77298440e101a58132fa348c3f896493b418c21a21bb54faad506a7fbc2c35c8cd2f6cae0dd9e61a1186394cc918e233e2c2f594571b
• Download URL:
  https://stacks.cdc.gov/view/cdc/215962/cdc_215962_DS1.pdf
• File Type:
  [PDF - 1.48 MB ]