Circadian rhythm disturbance induces osteoarthritis in mice: Involvement of Clock and Bmal1 dysregulation and Pdgfa inhibition

Circadian rhythm disturbance (CRD) for 70 days led to significant osteoarthritis-like symptoms in mice.

• CRD is likely associated with impaired bone development and the progression of osteoarthritis.
• Reduced expression of Clock and Bmal1 was observed in mice experiencing CRD.
• Upregulation of either Clock or Bmal1 decreased inflammatory cytokines IL-1β and IL-6, and mitigated cartilage erosion.
• The Clock:Bmal1 complex binds to a specific enhancer to promote Pdgfa transcription.
• Knockdown of Pdgfa reversed the protective effects of Clock and Bmal1 by inhibiting key signaling pathways.

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