Mechanical stretch induced calcium efflux from bone matrix stimulates osteoblasts

Area of Science:

• Biomedical Engineering
• Cell Biology
• Skeletal Biology

Background:

• Mechanisms of bone mechanosensing are debated.
• Current models lack real-time monitoring and neglect bone matrix alterations.
• In vitro studies often use non-bone substrates.

Purpose of the Study:

• Investigate real-time cellular response to bone microdamage.
• Explore the role of bone matrix in mechanotransduction.
• Identify signaling pathways involved in bone repair initiation.

Main Methods:

• Utilized devitalized bone matrix with induced post-yield strains.
• Measured spontaneous calcium ion (Ca(2+)) efflux from strained bone.
• Seeded bone samples with MC3T3-E1 osteoblasts to monitor intracellular calcium signaling.
• Repeated experiments using demineralized bone substrates to assess calcium's role.

Main Results:

• Demonstrated spontaneous Ca(2+) efflux (1.924±0.742 pmol cm(-2)s(-1)) from strained bone matrix.
• Observed strain-induced Ca(2+) efflux elicited osteoblast response, activating intracellular calcium signaling (52%±27% fluorescence increase).
• Confirmed the necessity of extracellular calcium, as signaling diminished with demineralized substrates (6%±10% fluorescence increase).

Conclusions:

• Proposed bone matrix as a mechanochemical transducer, converting mechanical strain into pericellular calcium signals.
• Highlighted pericellular calcium as a key signal for osteoblast response to mechanical loading.
• Suggested this mechanism may initiate bone repair at sites of critical deformation.