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PloS one2018; 13(6); e0197459; doi: 10.1371/journal.pone.0197459

Bone formation transcripts dominate the differential gene expression profile in an equine osteoporotic condition associated with pulmonary silicosis.

Abstract: Osteoporosis has been associated with pulmonary silicosis in California horses exposed to soils rich in cytotoxic silica dioxide crystals, a syndrome termed silicate associated osteoporosis (SAO). The causal mechanism for the development of osteoporosis is unknown. Osteoporotic lesions are primarily located in bone marrow-rich sites such as ribs, scapula and pelvis. Gene transcription patterns within bone marrow and pulmonary lymph nodes of affected horses may offer clues to disease pathobiology. Bone marrow core and tracheobronchial lymph node tissue samples harvested postmortem from affected and unaffected horses were examined histologically and subjected to RNA sequencing (RNA-seq). Sequenced data were analyzed for differential gene expression and gene ontology. Metatranscriptomic and metagenomic assays evaluated samples for infectious agents. Thirteen of 17 differentially expressed transcripts in bone marrow were linked to bone and cartilage formation such as integrin binding bone sialoprotein (log2FC = 3.39, PFDR = 0.013) and chondroadherin (log2FC = 4.48, PFDR = 0.031). Equus caballus solute carrier family 9, subfamily A2 (log2FC = 3.77, PFDR = 0.0034) was one of the four differentially expressed transcripts linked to osteoclast activity. Osteoblasts were hyperplastic and hypertrophic in bone marrow from affected horses. Biological pathways associated with skeletal morphogenesis were significantly enriched in affected horses. The 30 differentially expressed genes in affected lymph nodes were associated with inflammatory responses. Evidence of infectious agents was not found. The SAO affected bone marrow molecular signature demonstrated increased transcription and heightened activation of osteoblasts. Increased osteoblastic activity could be part of the pathological mechanism for osteoporosis or a compensatory response to the accelerated osteolysis. Transcriptome data offer gene targets for inquiries into the role of osteocytes and osteoblasts in SAO pathogenesis. Viral or bacterial infectious etiology in SAO is less likely based on metatranscriptomic and metagenomic data but cannot be completely ruled out.
Publication Date: 2018-06-01 PubMed ID: 29856822PubMed Central: PMC5983561DOI: 10.1371/journal.pone.0197459Google Scholar: Lookup
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  • Journal Article
  • Research Support
  • Non-U.S. Gov't

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

This research focuses on understanding the genetic and physiological changes that cause osteoporosis in horses affected by pulmonary silicosis, a condition also referred to as silicate associated osteoporosis (SAO). The researchers found significant alterations in gene expression related to bone and cartilage formation, suggesting changes in osteoblast activity could underlie the disease.

Research Methodology

  • The researchers aimed to understand the cause of osteoporosis in horses suffering from pulmonary silicosis, a disease that particularly impacts horses in California exposed to soils rich in cytotoxic silica dioxide crystals.
  • They examined gene transcription patterns within bone marrow and pulmonary lymph nodes of affected and unaffected horses. By comparing these patterns, they aimed to reveal potential clues to how the disease develops.
  • Bone marrow core and tracheobronchial lymph node tissue samples, harvested from deceased horses, were examined using RNA sequencing (RNA-seq). The data were then analyzed for differential gene expression and gene ontology.
  • The researchers also carried out metatranscriptomic and metagenomic assays. These evaluate samples for the presence of infectious agents.

Study Findings

  • Most of the differentially expressed transcripts in the bone marrow were connected to bone and cartilage formation. These included genes such as integrin binding bone sialoprotein and chondroadherin.
  • Increased osteoblastic activity (the cells responsible for bone formation) was observed in the bone marrow of affected horses. This suggests a pathogenesis role of osteoblasts in SAO.
  • The highest differential expression in the lymph nodes was linked to inflammatory responses.
  • Interestingly, no evidence of infectious agents, such as viral or bacterial pathogens, was found in the samples. This suggests that an infectious etiology in SAO is less likely, based on the presented data.

Implications and Future Research

  • Results emphasized that changes in the activity of osteoblasts, which help to build bone material, could be part of the disease mechanism causing osteoporosis, or perhaps a compensatory response to increased bone breakdown, known as osteolysis.
  • The study provided target genes for future inquiries, particularly about the role of osteoblasts and another type of bone cell called osteocytes in relation to SAO.
  • Even though the study did not find evidence of pathogens, this possibility cannot be ruled out entirely, keeping the door open for future investigations.

Cite This Article

APA
Zavodovskaya R, Stover SM, Murphy BG, Katzman S, Durbin-Johnson B, Britton M, Finno CJ. (2018). Bone formation transcripts dominate the differential gene expression profile in an equine osteoporotic condition associated with pulmonary silicosis. PLoS One, 13(6), e0197459. https://doi.org/10.1371/journal.pone.0197459

Publication

ISSN: 1932-6203
NlmUniqueID: 101285081
Country: United States
Language: English
Volume: 13
Issue: 6
Pages: e0197459
PII: e0197459

Researcher Affiliations

Zavodovskaya, Regina
  • Department of Anatomy, Physiology and Cell Biology, UC Davis School of Veterinary Medicine, University of California, Davis, California, United States of America.
Stover, Susan M
  • Department of Anatomy, Physiology and Cell Biology, UC Davis School of Veterinary Medicine, University of California, Davis, California, United States of America.
Murphy, Brian G
  • Department of Pathology, Microbiology and Immunology, UC Davis School of Veterinary Medicine, University of California, Davis, California, United States of America.
Katzman, Scott
  • Department of Surgical & Radiological Sciences, UC Davis School of Veterinary Medicine, University of California, Davis, California, United States of America.
Durbin-Johnson, Blythe
  • Department of Public Health Sciences, UC Davis School of Medicine, University of California, Davis, Davis, California, United States of America.
Britton, Monica
  • UC Davis Genome Center, Bioinformatics Core Facility, University of California, Davis, Davis, California, United States of America.
Finno, Carrie J
  • Department of Population Health & Reproduction, UC Davis School of Veterinary Medicine, University of California, Davis, California, United States of America.

MeSH Terms

  • Animals
  • Bone Marrow Cells / metabolism
  • Bone Marrow Cells / pathology
  • California
  • Horse Diseases / genetics
  • Horse Diseases / pathology
  • Horses / genetics
  • Inflammation / genetics
  • Inflammation / pathology
  • Lymph Nodes / metabolism
  • Lymph Nodes / pathology
  • Osteoblasts / metabolism
  • Osteoblasts / pathology
  • Osteoclasts / metabolism
  • Osteoclasts / pathology
  • Osteogenesis / genetics
  • Osteoporosis / genetics
  • Sequence Analysis, RNA
  • Transcription, Genetic
  • Transcriptome / genetics

Grant Funding

  • K01 OD015134 / NIH HHS
  • L40 TR001136 / NCATS NIH HHS
  • T32 OD011147 / NIH HHS

Conflict of Interest Statement

The authors have declared that no competing interests exist.

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Citations

This article has been cited 2 times.
  1. Lee S, Baker ME, Clinton M, Taylor SE. Use of Omics Data in Fracture Prediction; a Scoping and Systematic Review in Horses and Humans. Animals (Basel) 2021 Mar 30;11(4).
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