IL-1beta decreases the elastic modulus of human tenocytes.
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-1beta (IL-1beta) would modulate intracellular cytoskeleton polymerization and regulate cell stiffness. The purpose of this study was to investigate the utility of IL-1beta to alter the Young's modulus of human tenocytes. Young's modulus is the ratio of the stress to the strain, E = stress/strain = (F/A)/(deltaL/L0), where L0 is the equilibrium length, deltaL 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-1beta for 5 days. The Young's modulus was reduced by 27-63%. Actin filaments were disrupted in >75% of IL-1beta-treated cells, resulting in a stellate shape. In contrast, immunostaining of alpha-tubulin showed increased intensity in IL-1beta-treated tenocytes. Human tenocytes in IL-1beta-treated bioartificial tendons were more tolerant to mechanical loading than were untreated counterparts. These results indicate that IL-1beta reduced the Young's modulus of human tenocytes by disrupting the cytoskeleton and/or downregulating the expression of actin and upregulating 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.
Qi
Jie
J
Flexcell International Corp., 437 Dimmocks Mill Rd., Suite 28, Hillsborough, North Carolina 27278, USA.
Fox
Ann Marie
AM
Alexopoulos
Leonidas G
LG
Chi
Liqun
L
Bynum
Donald
D
Guilak
Farshid
F
Banes
Albert J
AJ
D008841:Actin Cytoskeleton / Q000737:chemistry / Q000187:drug effects / Q000502:physiology; D000199:Actins / Q000378:metabolism; D000368:Aged; D000369:Aged, 80 and over; D001696:Biomechanical Phenomena; D048430:Cell Shape / Q000187:drug effects* / Q000502:physiology*; D002470:Cell Survival / Q000502:physiology; D002478:Cells, Cultured; D002675:Child, Preschool; D004548:Elasticity / Q000187:drug effects; D005260:Female; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D005786:Gene Expression Regulation / Q000502:physiology; D006801:Humans; D007375:Interleukin-1 / Q000502:physiology*; D008297:Male; D008870:Microtubules / Q000737:chemistry / Q000187:drug effects / Q000502:physiology; D013710:Tendons / Q000166:cytology* / Q000187:drug effects / Q000502:physiology; D014404:Tubulin / Q000378:metabolism; D016474:Weight-Bearing
D000199:Actins; D007375:Interleukin-1; D014404:Tubulin