title: Oscillatory tension differentially modulates matrix metabolism and cytoskeletal organization in chondrocytes and fibrochondrocytes.
abstract: Several modes of mechanical stimulation, including compression, shear, and hydrostatic pressure, have been shown to modulate chondrocyte matrix synthesis, but the effects of mechanical tension have not been widely explored. Since articular cartilage is primarily loaded in compression, tension is not generally viewed as a major contributor to the stress state of healthy tissue. However, injury or attempted repair may cause tension to become more significant. Additionally, fibrocartilaginous tissues experience significant tensile stresses in their normal mechanical environment. In this study we investigated mechanical tension as a means to modulate matrix synthesis and cytoskeletal organization in bovine articular chondrocytes and meniscal fibrochondrocytes (MFCs) in a three-dimensional fibrin construct culture system. Oscillatory tension was applied to constructs at 1.0 Hz and 0-10% displacement variation using a custom device. For nearly all conditions and both cell types, oscillatory tension inhibited matrix synthesis as indicated by 3H-proline and 35S-sulfate incorporation. Additionally, oscillatory tension significantly increased proliferation by chondrocytes but not MFCs. Confocal imaging revealed that all cells initially displayed a rounded morphology, but over time MFCs spontaneously developed a three-dimensional, stellate morphology with numerous projections containing organized cytoskeletal filaments. Interestingly, while unloaded chondrocytes remained rounded, chondrocytes subjected to oscillatory tension developed a similar stellate morphology. Both the biochemical and morphological results of this study have important implications for successfully developing cartilage and fibrocartilage tissue replacements and repair strategies.
authors.affiliation: George W. Woodruff School of Mechanical Engineering, Parker H. Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, GA 30332, USA.
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Vanderploeg
authors.forename: Stacy M
authors.initials: SM
authors.lastname: Imler
authors.forename: Kathryn R
authors.initials: KR
authors.lastname: Brodkin
authors.forename: Andrés J
authors.initials: AJ
authors.lastname: García
authors.forename: Marc E
authors.initials: ME
authors.lastname: Levenston
mesh_terms: D000818:Animals; D001696:Biomechanical Phenomena / Q000295:instrumentation / Q000706:statistics & numerical data; D002358:Cartilage, Articular / Q000166:cytology / Q000378:metabolism; D002417:Cattle; D002478:Cells, Cultured; D019902:Chondrocytes / Q000166:cytology / Q000378:metabolism*; D003599:Cytoskeleton / Q000378:metabolism*; D005109:Extracellular Matrix / Q000378:metabolism*; D008592:Menisci, Tibial / Q000166:cytology / Q000378:metabolism; D013314:Stress, Mechanical; D013718:Tensile Strength