Initial Stress-Kick Is Required for Fluid Shear Stress-Induced Rate Dependent Activation of Bone Cells

Annals of Biomedical Engineering, Vol. 33, No. 1, January 2005 (2005) pp. 104110

Initial Stress-Kick Is Required for Fluid Shear Stress-Induced Rate Dependent Activation of Bone Cells

ROMMEL G. BACABAC,1 THEO H. SMIT,2 MARGRIET G. MULLENDER,1 JACK J. W. A. VAN LOON,1,3 and Jenneke Klein-Nulend1

1Department of Oral Cell Biology, Academic Centre for Dentistry Amsterdam, Vrije Universiteit, Amsterdam, The Netherlands;

2Department of Clinical Physics and Informatics, Vrije Universiteit Medical Center, Amsterdam, The Netherlands; and 3Dutch Experiment Support Center, Vrije Universiteit, Amsterdam, The Netherlands

(Received 6 February 2004; accepted 16 August 2004)

AbstractThe shear stress induced by the loading-mediated ow of interstitial uid through the lacunocanalicular network is a likely stimulus for bone cell adaptive responses. Furthermore, the magnitude of the cellular response is related to the rate of mechanical loading rather than its magnitude. Thus, bone cells might be very sensitive to sudden stress-kicks, as occuring e.g., during impact loading. There is evidence that cells change stiffness under stress, which might make them more sensitive to subsequent loading. We studied the inuence of a stress-kick on the mechanosensitivity of MC3T3-E1 osteoblast-like cells under different peak shear rate conditions, as measured by nitric oxide production. MC3T3-E1 bone cells were treated with steady or pulsating uid shear stress (PFSS) for 5 min with different peak rates (9.70, 17.5, and22.0 Pa Hz) using varying frequencies (5 and 9 Hz), and amplitudes(0.70 and 0.31 Pa). PFSS treatment was done with or without uid ow pretreatment phase, which removed the initial stress-kick by rst applying a slow uid ow increase. Nitric oxide production in response to uid shear stress was rate dependent, but necessitated an initial stress-kick to occur. This suggests that high-rate stimuli condition bone cells to be more sensitive for high-frequency, low-amplitude loads.

KeywordsMC3T3-E1, Osteoblasts, Fluid ow, Fluid shear stress rate, Mechanical loading, Nitric oxide, Parallel-plate chamber, Bone formation, Microgravity.

INTRODUCTION

During life, bones adapt their mass and structure to the prevailing mechanical loads, in order to resist mechanical failure with minimum material expense. It is currently believed that this process of adaptation is governed by osteocytes, which respond to the loading-induced ow of inter-stitial uid through the lacuno-canalicular network.6 When bones are loaded, the resultingdeformation will drive the

Address correspondence to Jenneke Klein-Nulend, PhD, ACTA-Vrije Universiteit, Deptartment...