Mechanical stretch induced calcium efflux from bone matrix stimulates osteoblasts.
The mechanisms by which bone cells sense critically loaded regions of bone are still a matter of ongoing debate. Animal models to investigate response to microdamage involve post mortem immunohistological analysis and do not allow real-time monitoring of cellular response during the emergence of the damage in bone. Most in vitro mechanical stimulation studies are conducted on non-bone substrates, neglecting the damage-related alterations in the pericellular niche and their potential effects on bone cells. The current study reports spontaneous efflux of calcium ions (Ca(2+)) (1.924±0.742 pmol cm(-2)s(-1)) from regions of devitalized bone matrix undergoing post-yield strains, induced by a stress concentrator. When these samples are seeded with MC3T3-E1 osteoblasts, the strain-induced Ca(2+) efflux from bone elicits cell response at the stress concentration site as manifested by activation of intracellular calcium signaling (increase in fluorescence by 52%±27%). This activity is associated with extracellular calcium because the intracellular calcium signaling in response to mechanical loading subsides when experiments are repeated using demineralized bone substrates (increase in fluorescence by 6%±10%). These results imply a novel perspective where bone matrix acts as an intermediary mechanochemical transducer by converting mechanical strain into a chemical signal (pericellular calcium) to which cells respond. Such a mechanism may be responsible for triggering repair at locations of bone matrix undergoing critical deformation levels.
Weldon School of Biomedical Engineering, Purdue University, West Lafayette, IN 47907, USA. xuanhao@purdue.edu
Xuanhao
X
Sun
Eric
E
McLamore
Vipuil
V
Kishore
Kateri
K
Fites
Mikhail
M
Slipchenko
D Marshall
DM
Porterfield
Ozan
O
Akkus
D000818:Animals; D001857:Bone Matrix / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D002417:Cattle; D005269:Femur / Q000378:metabolism*; D010006:Osteoblasts / Q000378:metabolism*; D013314:Stress, Mechanical
D002118:Calcium