PHYSIOLOGICAL LEVELS OF SUBSTRATE DEFORMATION ARE LESS STIMULATORY TO BONE CELLS COMPARED TO FLUID FLOW

Jun You, Clare E. Yellowley, Henry J. Donahue, Christopher R. Jacobs

Research output: Chapter in Book/Report/Conference proceedingConference contribution

Abstract

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.

Original languageEnglish (US)
Title of host publicationAdvances in Bioengineering
PublisherAmerican Society of Mechanical Engineers (ASME)
Pages161-162
Number of pages2
ISBN (Electronic)9780791816400
DOIs
StatePublished - 1999
Externally publishedYes
EventASME 1999 International Mechanical Engineering Congress and Exposition, IMECE 1999 - Nashville, United States
Duration: Nov 14 1999Nov 19 1999

Publication series

NameASME International Mechanical Engineering Congress and Exposition, Proceedings (IMECE)
Volume1999-D

Conference

ConferenceASME 1999 International Mechanical Engineering Congress and Exposition, IMECE 1999
Country/TerritoryUnited States
CityNashville
Period11/14/9911/19/99

ASJC Scopus subject areas

  • Mechanical Engineering

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