title: Tissue shear deformation stimulates proteoglycan and protein biosynthesis in bovine cartilage explants.
abstract: Chondrocytes are known to sense and respond to mechanical and physicochemical stimuli by multiple regulatory pathways, including upstream signaling, transcription, translation, posttranslational modifications, and vesicular transport. Due to the complexity of identifying the biophysical phenomena that occur during cartilage loading in vivo, the regulatory mechanisms that govern chondrocyte mechanotransduction are not fully understood. Recent studies have shown that fluid flow during dynamic compression of cartilage explants can stimulate proteoglycan and protein synthesis. In this study, we examined the effect of deformations of cell and extracellular matrix on chondrocyte biosynthesis. We used tissue shear loading, since tissue shear causes little volumetric deformation and can thereby decouple fluid flow from cell and matrix deformation. Shear loading was applied over a wide range of frequencies, 0.01-1.0 Hz, using 1-3% sinusoidal shear strain amplitudes, and the resulting proteoglycan and protein syntheses were measured using radiolabel incorporation. In addition, quantitative autoradiography was used to investigate spatial variations in matrix biosynthesis and to correlate these variations with the spatial profiles of biophysical stimuli. Our data show that tissue shear loading at 1-3% strain amplitude stimulated the synthesis of protein by approximately 50% and proteoglycans by approximately 25% at frequencies between 0.01 and 1.0 Hz. The relatively uniform patterns of biosynthesis in the radial and vertical directions within cylindrical explants revealed by autoradiography suggest that the stimulatory effect was associated with the relatively uniform deformation caused by simple shear loading. These results suggest that chondrocytes can respond to tissue shear stress-initiated pathways for the production of collagen and proteoglycan, which include deformation of cells and pericellular matrix, even in the absence of macroscopic tissue-level fluid flow.
authors.affiliation: Continuum Electromechanics Group, Department of Electrical Engineering and Computer Science, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA. msjin@mit.edu
authors.forename: M
authors.initials: M
authors.lastname: Jin
authors.forename: E H
authors.initials: EH
authors.lastname: Frank
authors.forename: T M
authors.initials: TM
authors.lastname: Quinn
authors.forename: E B
authors.initials: EB
authors.lastname: Hunziker
authors.forename: A J
authors.initials: AJ
authors.lastname: Grodzinsky
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001345:Autoradiography; D002356:Cartilage / Q000378:metabolism*; D002417:Cattle; D066298:In Vitro Techniques; D010812:Physical Stimulation / Q000295:instrumentation / Q000379:methods; D011392:Proline / Q000032:analysis / Q000378:metabolism; D014176:Protein Biosynthesis; D011509:Proteoglycans / Q000096:biosynthesis; D013314:Stress, Mechanical; D013431:Sulfates / Q000032:analysis / Q000378:metabolism
chemical_list: D011509:Proteoglycans; D013431:Sulfates; D011392:Proline