TY - GEN
T1 - PHYSIOLOGICAL LEVELS OF SUBSTRATE DEFORMATION ARE LESS STIMULATORY TO BONE CELLS COMPARED TO FLUID FLOW
AU - You, Jun
AU - Yellowley, Clare E.
AU - Donahue, Henry J.
AU - Jacobs, Christopher R.
N1 - Funding Information:
This work was supported by the Whitaker Foundation, NIH RR11769 & AG 13087 and The U.S. Army.
Funding Information:
This work was supported by the Whitaker Foundation, NIH RRl 1769 & AG 13087 and The U.S. Army.
Publisher Copyright:
© 1999 American Society of Mechanical Engineers (ASME). All rights reserved.
PY - 1999
Y1 - 1999
N2 - It is believed that bone cells can sense mechanical loading and alter bone external shape and internal structure to efficiently support the load bearing demands placed upon it. However, the mechanism by which bone cells sense and respond to their mechanical environment is still poorly understood. In particular, the load-induced signals to which bone cells respond, e.g. fluid flow, substrate deformation, electrokinetic effects etc., are unclear. Furthermore, there are few studies focused on the effects of physiological strain (strain< 0.5%, Burr, 1996; Owan, 1997) on bone cells. The goal of this study was to investigate cytosolic Ca2+mobilization (a very early signaling event) in response to different substrate strains (physiological or supraphysiological strains), and to distinguish the effects of substrate strain from those of fluid flow by applying precisely controlled strain without induced fluid flow. In addition, we quantified the effect of physiologically relevant fluid flow (Cowin, 1995) and substrate stretch on the expression of mRNA for the bone matrix protein osteopontin (OPN). A computer controlled stretch device was employed to apply different substrate strains, 0.1%, 1%, 5% and 10%. A parallel plate flow chamber was used to test cell responses to steady and oscillating flows (20dyn/cm2, 1Hz). Our data demonstrate that physiological strain (<0.5%) does not induce [Ca2+]iiresponses in primary rat osteoblastic cells (ROB) in vitro. However, there was a significant (p<0.05) increase in the number of responding cells at supraphysiological strains of 1, 5, and 10% suggesting that the cells were capable of a biological response. Similar results for human fetal osteoblastic cells (hFOB 1.19) and osteocyte-like cells (MLO-Y4) were obtained. Furthermore, compared to physiological substrate deformation, physiological fluid flow induced greater [Ca2+]iresponses for hFOB cells, and these [Ca2+]iresponses were quantitatively similar to those obtained for 10% substrate strain. Moreover we found no change in osteopontin mRNA expression after 0.5% strain stretch. Conversely, physiological oscillating flow (20dyn/cm2, 1Hz) caused a significant increase in osteopontin mRNA. These data suggest that, relative to fluid flow, substrate deformation may play less of a role in bone cell mechanotransduction.
AB - It is believed that bone cells can sense mechanical loading and alter bone external shape and internal structure to efficiently support the load bearing demands placed upon it. However, the mechanism by which bone cells sense and respond to their mechanical environment is still poorly understood. In particular, the load-induced signals to which bone cells respond, e.g. fluid flow, substrate deformation, electrokinetic effects etc., are unclear. Furthermore, there are few studies focused on the effects of physiological strain (strain< 0.5%, Burr, 1996; Owan, 1997) on bone cells. The goal of this study was to investigate cytosolic Ca2+mobilization (a very early signaling event) in response to different substrate strains (physiological or supraphysiological strains), and to distinguish the effects of substrate strain from those of fluid flow by applying precisely controlled strain without induced fluid flow. In addition, we quantified the effect of physiologically relevant fluid flow (Cowin, 1995) and substrate stretch on the expression of mRNA for the bone matrix protein osteopontin (OPN). A computer controlled stretch device was employed to apply different substrate strains, 0.1%, 1%, 5% and 10%. A parallel plate flow chamber was used to test cell responses to steady and oscillating flows (20dyn/cm2, 1Hz). Our data demonstrate that physiological strain (<0.5%) does not induce [Ca2+]iiresponses in primary rat osteoblastic cells (ROB) in vitro. However, there was a significant (p<0.05) increase in the number of responding cells at supraphysiological strains of 1, 5, and 10% suggesting that the cells were capable of a biological response. Similar results for human fetal osteoblastic cells (hFOB 1.19) and osteocyte-like cells (MLO-Y4) were obtained. Furthermore, compared to physiological substrate deformation, physiological fluid flow induced greater [Ca2+]iresponses for hFOB cells, and these [Ca2+]iresponses were quantitatively similar to those obtained for 10% substrate strain. Moreover we found no change in osteopontin mRNA expression after 0.5% strain stretch. Conversely, physiological oscillating flow (20dyn/cm2, 1Hz) caused a significant increase in osteopontin mRNA. These data suggest that, relative to fluid flow, substrate deformation may play less of a role in bone cell mechanotransduction.
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U2 - 10.1115/IMECE1999-0427
DO - 10.1115/IMECE1999-0427
M3 - Conference contribution
AN - SCOPUS:85122705850
T3 - ASME International Mechanical Engineering Congress and Exposition, Proceedings (IMECE)
SP - 161
EP - 162
BT - Advances in Bioengineering
PB - American Society of Mechanical Engineers (ASME)
T2 - ASME 1999 International Mechanical Engineering Congress and Exposition, IMECE 1999
Y2 - 14 November 1999 through 19 November 1999
ER -