Hypertrophy and physiological death of equine chondrocytes in vitro.
Authors: Ahmed Y A, Tatarczuch L, Pagel C N, Davies H M, Mirams M, Mackie E J
Journal: Equine veterinary journal
Summary
Osteochondrosis in horses stems from disrupted endochondral ossification during skeletal development, a process normally involving precisely coordinated chondrocyte proliferation, hypertrophy and apoptosis; until this 2007 work, no robust in vitro model existed to study these mechanisms specifically in equine cells. Ahmed and colleagues cultured chondrocytes isolated from horses of varying ages as three-dimensional pellets in different serum conditions, using microscopy and quantitative PCR to characterise morphological changes and gene expression patterns across the ossification pathway. Fetal chondrocyte pellets successfully recapitulated in vivo hypertrophy and death, whilst cells from foals older than five months failed to hypertrophy and instead formed aberrant inclusion bodies; neonatal cells cultured in horse serum—rather than fetal calf serum—achieved hypertrophy, though with some inclusion body formation. Gene expression profiling revealed coordinated temporal increases in Sox9, collagen type II, Runx2, matrix metalloproteinase-13 and connective tissue growth factor, alongside declining fibroblast growth factor receptor-3 and vascular endothelial growth factor expression. This fetal chondrocyte pellet culture system offers equine researchers a physiologically relevant platform for investigating osteochondrosis pathogenesis, potentially identifying intervention targets during critical growth phases when the disease typically emerges.
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Practical Takeaways
- •This in vitro model provides a validated system for studying osteochondrosis mechanisms in horses, potentially leading to better understanding of growth cartilage disorders in young horses
- •The age-dependent differences in chondrocyte behavior suggest that osteochondrosis pathogenesis may involve distinct cellular mechanisms in fetal versus postnatal development
- •Research using this culture system may eventually inform prevention and treatment strategies for osteochondrosis, a significant cause of lameness in growing horses
Key Findings
- •Fetal equine chondrocytes cultured as pellets undergo hypertrophy and physiological death morphologically similar to in vivo processes
- •Chondrocytes from horses >5 months old do not undergo hypertrophy in pellet culture and instead form intramembranous inclusion bodies
- •Neonatal foal chondrocytes cultured in horse serum (HS) undergo hypertrophy while those in fetal calf serum (FCS) resemble older horse cultures
- •Fetal chondrocyte pellets express cartilage markers (collagen II, aggrecan) with sequential increases in Sox9, Runx2, MMP-13, and CTGF mRNA during culture