Bone formation transcripts dominate the differential gene expression profile in an equine osteoporotic condition associated with pulmonary silicosis.
Authors: Zavodovskaya Regina, Stover Susan M, Murphy Brian G, Katzman Scott, Durbin-Johnson Blythe, Britton Monica, Finno Carrie J
Journal: PloS one
Summary
Silicate-associated osteoporosis (SAO) in Californian horses exposed to silica-rich soils produces severe bone loss concentrated in marrow-rich sites including ribs, scapulae and pelvis, yet its underlying mechanism remains unclear. Researchers conducted postmortem bone marrow and tracheobronchial lymph node sampling from affected and unaffected horses, performing histological examination and RNA sequencing to identify differential gene expression patterns and associated biological pathways, whilst also screening for infectious agents. The bone marrow from affected horses showed significantly upregulated transcription of 13 bone and cartilage formation genes—including integrin binding bone sialoprotein (fold-change 3.39) and chondroadherin (fold-change 4.48)—alongside suppressed osteoclast-related genes, with histology revealing hyperplastic and hypertrophic osteoblasts; conversely, lymph nodes displayed 30 differentially expressed genes related to inflammatory responses, though no infectious agents were detected. This paradoxical pattern of heightened osteoblastic activity alongside bone loss suggests either compensatory bone formation attempting to offset accelerated bone resorption, or abnormal osteoblast function directly contributing to pathology—a distinction with significant implications for therapeutic targeting. For practitioners, these findings indicate that SAO pathogenesis involves dysregulated bone cell activity rather than infection, and point toward osteocyte and osteoblast function as critical targets for understanding disease progression and developing interventions to preserve skeletal integrity in affected horses.
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Practical Takeaways
- •SAO in California horses involves abnormal osteoblast activation and bone formation dysregulation rather than infectious disease; consider environmental silica exposure as a risk factor in affected regions
- •The condition primarily affects bone marrow-rich sites (ribs, scapula, pelvis), so monitor these areas clinically in at-risk horses
- •Understanding the molecular basis of SAO may eventually guide targeted therapeutic interventions targeting osteoblast or osteoclast pathways, though current clinical management remains supportive
Key Findings
- •Bone marrow from SAO-affected horses showed 13 of 17 differentially expressed transcripts linked to bone and cartilage formation, with integrin binding bone sialoprotein upregulated 10.3-fold and chondroadherin upregulated 22.6-fold
- •Osteoblasts in affected bone marrow were hyperplastic and hypertrophic with heightened transcriptional activation
- •Biological pathways associated with skeletal morphogenesis were significantly enriched in affected horses
- •No infectious agents (viral or bacterial) were detected via metatranscriptomic and metagenomic analysis