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Chrono-mechanobiology: The Complex Interactions Between Mechanotransduction and Circadian Rhythms in the Intervertebral Disc and Articular Cartilage, in Health and Disease
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DOI：10.1016/j.plrev.2026.03.004.png)
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Abstract
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• Mechanical stress is transduced into biochemical signals in intervertebral disc and articular cartilage via direct and indirect pathways, shaping transcriptional programs that govern extracellular matrix homeostasis and the balance between tissue maintenance and degeneration. • Circadian clocks in intervertebral disc and articular cartilage coordinate rhythmic regulation of extracellular matrix turnover, nutrient transport, metabolism, and inflammation, while their disruption predisposes tissues to degeneration. • Mechanical cues act as potent zeitgebers that entrain circadian rhythms, whereas circadian clocks modulate mechanosensitivity, aligning cellular responses with daily cycles of loading and rest. • The bidirectional crosstalk between mechanotransduction and circadian rhythms emerges as a central determinant of intervertebral disc and articular cartilage health, and its disruption contributes to intervertebral disc degeneration and osteoarthritis. • Chrono-informed and mechanobiology-based strategies provide promising opportunities to prevent or treat intervertebral disc and articular cartilage degeneration through optimized timing of interventions.
Keywords:
Intervertebral Disc
Articular Cartilage
Mechanotransduction
Circadian Rhythm
Chronobiology
Chronomechanobiology
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