Piezo1 controls new mitochondria formation through energy sensors to reduce bone loss in inactivity-related osteoporosis

Significant downregulation of Piezo1 expression was observed in bone tissue and bone marrow-derived stem cells during disuse osteoporosis.

• Disuse osteoporosis is characterized by progressive bone mass loss and microarchitectural weakening due to insufficient mechanical loading.
• The Piezo1 ion channel plays a critical role in maintaining bone health by responding to mechanical signals.
• In a mouse model of microgravity-induced bone loss, systemic administration of the Piezo1 agonist Yoda1 reduced osteopenia and enhanced bone formation.
• Activation of Piezo1 in bone marrow-derived stem cells led to increased mitochondrial biogenesis and improved cell function.
• The protective effects of Piezo1 activation were dependent on specific signaling pathways involving AMPK and SIRT1.
• Inhibition of SIRT1 negated the benefits of Piezo1 activation, indicating its essential role in maintaining bone integrity under mechanical stress.

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