Submitted on September 9, 2005
Accepted on March 7, 2006
IL-1&bgr; decreases the elastic modulus of human tenocytes
Jie Qi1, Ann M Fox2, Leonidas G Alexopoulos3, Liqun Chi4, Donald K Bynum5, Farshid Guilak3, and Albert J Banes6*
1 Flexcell International Corporation, Hillsborough, North Carolina, United States; Joint Department of Biomedical Engineering, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States
2 Joint Department of Biomedical Engineering, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States
3 Orthopaedic Research Laboratories Departments of Surgery and Biomedical Engineering, Duke University Medical Center, Durham, North Carolina, United States
4 Flexcell International Corporation, Hillsborough, North Carolina, United States
5 Orthopaedics, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States
6 Flexcell International Corporation, Hillsborough, North Carolina, United States; Joint Department of Biomedical Engineering, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States; Applied and Materials Sciences, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States
* To whom correspondence should be addressed. E-mail: ajbvault{at}med.unc.edu.
Cellular responses to mechanical stimuli are regulated by interactions with the extracellular matrix, which in turn are strongly influenced by the degree of cell stiffness (Young's modulus). It was hypothesized that a more elastic cell could better withstand the rigors of remodeling and mechanical loading. It was further hypothesized that interleukin-1
(IL-1) would modulate intracellular cytoskeleton and regulate cell stiffness. The purpose of this study was to investigate the utility of IL-1 to alter the Young's modulus of human tendon internal fibroblasts. Young's modulus is the ratio of the stress to the strain, E= stress/strain=(F/A)/(
L/L0), where L0 is the equilibrium length, L is the length change under the applied stress, F is the force applied, and A is the area over which the force is applied. Human tenocytes were incubated with 100 pM recombinant human IL-1 for 5 days. The Young's modulus of IL-1-treated tenocytes was reduced by 27 - 63%. Actin filaments were disrupted in more than 75% of IL-1-treated cells, resulting in a stellate cell shape. In contrast, immunostaining of 
-tubulin showed increased intensity in IL-1-treated tenocytes. Human tenocytes in IL-1-treated bioartificial tendons (BATs) were more tolerant to mechanical loading than were untreated counterparts. These results indicate that IL-1 reduced the Young's modulus of human tenocytes by disrupting the cytoskeleton and/or down-regulating the expression of actin and up-regulating the expression of tubulins. The reduction in cell modulus may help cells to survive excessive mechanical loading that may occur in damaged or healing tendons.
