Transcriptomic and Functional Comparison of Cells Isolated From Healthy and Degenerated Ovine Intervertebral Discs

Area of Science:

• Biomedical Science
• Cell Biology
• Translational Medicine

Background:

• Intervertebral disc degeneration (IVDD) causes chronic low back pain, with mechanisms not fully understood.
• Sheep are a relevant model for IVDD due to anatomical and biomechanical similarities to humans.
• In vitro studies using annulus fibrosus (AF) and nucleus pulposus (NP) cells can provide insights into age-associated disc degeneration.

Purpose of the Study:

• To investigate how well sheep AF and NP cells in vitro capture senescence and metabolic changes seen in vivo.
• To assess the translational relevance of sheep disc cells by comparing their transcriptional profiles with human data.
• To evaluate the functional responses of young versus aged sheep disc cells under basal and stimulated conditions.

Main Methods:

• Transcriptomic profiling of AF and NP cells from young and aged sheep.
• Cross-species deconvolution analysis using human single-cell RNA-sequencing data.
• Functional assays assessing cell responses to inflammatory (IL-1β) and senescence-inducing stimuli.

Main Results:

• Aged sheep AF and NP cells exhibited distinct age- and tissue-specific transcriptional signatures, including upregulated inflammatory and senescence-associated genes.
• Transcriptional modules in aged sheep discs were conserved with human degenerated discs, supporting translational relevance.
• Despite molecular differences, young and aged sheep cells showed comparable functional responses under basal and pro-degenerative conditions.

Conclusions:

• Sheep AF and NP cells are a validated in vitro model for studying IVDD mechanisms and preclinical testing.
• Aged sheep cells reflect some molecular aspects of degeneration but do not offer additional functional benefits over young cells in vitro.
• The study validates the sheep model for IVDD research, highlighting conserved transcriptional pathways with human disease.