Cry2 prompts clock oscillation and temporomandibular joint homeostasis under mechanical loading

🎖️ Top 10% JournalJan 6, 2026Bone & joint research

Cry2 supports body clock rhythms and jaw joint balance during mechanical stress

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Circadian Biology on OpenScience ↗PubMed ↗DOI ↗OA ↗

Abstract

One-week static culture resulted in accelerated cartilage degeneration and diminished levels of core clock genes.

Mechanical loading is associated with maintaining the oscillations of circadian rhythm genes in temporomandibular joint cartilage.
Static culture for one week disrupted cartilage metabolism compared to one-day static culture.
Rhythmic mechanical loading partially preserved cartilage homeostasis over the same period.
Mechanical loading promoted the movement of Cry2 into the nucleus, which was influenced by Rho-associated protein kinase activation.
Inhibition of Rho-associated protein kinase led to decreased trafficking of Cry2, affecting circadian rhythm and cartilage health.

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AIMS: Cartilage metabolism exhibits (CR), and disruption of these often correlates with cartilage degeneration. Mechanical stimulation is a vital zeitgeber of CR in cartilage. However, the effects of mechanical loading on CR and cartilage homeostasis have not been explored. In this study, we aimed to explore the involvement of CR in mediating temporomandibular joint (TMJ) cartilage homeostasis under mechanical loading.

METHODS: We introduced the mechanical loading models of both rat TMJ chondrocytes and condyle explants. The mechanical loading was applied through rhythmic compression (12 hrs on and 12 hrs off), while the mechanical unloading model was set as control through static culture of cells and explants.

RESULTS: One-week static culture led to imbalanced cartilage metabolism and accelerated cartilage degeneration. This was accompanied by diminished levels of core clock genes (,,, and), compared with oscillations of these genes in one-day static cultured chondrocytes and condyle explants. Rhythmic physiological mechanical loading for one week not only sustained the oscillations of CR genes, but also partially maintained homeostasis of cartilage. The mechanistic delineation confirmed that one week of mechanical loading promoted the nuclear-cytoplasmic shuttling of Per1 and Cry2, which were obvious in one-day static cultured chondrocytes but weakened in one-week static cultured cells. Furthermore, nuclear translocation of Cry2, but not Per1, was dependent upon mechanical loading-induced Rho-associated protein kinase (ROCK) activation and actin polymerization. Inhibition of ROCK caused actin depolymerization and partially blocked Cry2 nuclear-cytoplasmic trafficking. Finally, down-regulation of Cry2 in both chondrocytes and condyle explants attenuated mechanical loading-sustained circadian oscillations and cartilage homeostasis. bmal1clock per1cry2

CONCLUSION: This study elucidated the involvement of CR in mediating mechanical loading-related cartilage homeostasis, as well as the critical role of ROCK-actin-Cry2 in regulating normal CR and homeostasis of TMJ cartilage under rhythmic mechanical loading.

Key numbers

Lower levels in one-week samples vs. one-day samples

Decrease in Collagen II and Levels

Measured in explants cultured for one week.

Higher levels in one-week samples vs. one-day samples

Increase in Levels

Observed in explants cultured for one week.

100 Kpa and 200 Kpa protect cartilage

Cyclic Mechanical Loading Magnitudes

Applied for one week in explants.

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