title: Dynamic compression stimulates proteoglycan synthesis by mesenchymal stem cells in the absence of chondrogenic cytokines.
abstract: The objective of this study was to evaluate the effect of dynamic compression on mesenchymal stem cell (MSC) chondrogenesis. Dynamic compression was applied to agarose hydrogels seeded with bone marrow-derived adult equine MSCs. In the absence of the chondrogenic cytokine transforming growth factor beta (TGFbeta), dynamic compression applied for 12 h per day led to significantly greater proteoglycan synthesis than in unloaded TGFbeta-free cultures, although at a rate that was approximately 20% to 35% of unloaded TGFbeta cultures. These data suggest that the emergence of aggrecan dominated a chondrogenic response to loading as increases in proteoglycan synthesis. Cross-sectional analyses were conducted to subjectively identify potential spatial distributions of heterogeneous differentiation. In loaded samples, cell viability and metachromatic staining was low near the porous compression platen interface but increased with depth, reaching levels in the lower portion of the hydrogel that resembled unloaded TGFbeta cultures. These results suggest that the combination of high hydrostatic pressure and low dynamic strain and fluid flow had a stronger effect on chondrogenesis than did low hydrostatic pressure coupled with high dynamic strain and fluid flow. Next, the 12-h per day loading protocol was applied in the presence of TGFbeta. Biosynthesis in loaded cultures was less than in unloaded TGFbeta samples. Taken together, these data suggest that the duration of loading necessary to stimulate mechanoinduction of MSCs may not be optimal for neo-tissue accumulation in the presence of chondrogenic cytokines.
authors.affiliation: Orthopaedic Research Center, Department of Clinical Science, Colorado State University, Fort Collins, Colorado 80523, USA. john.kisiday@colostate.edu
authors.forename: John D
authors.initials: JD
authors.lastname: Kisiday
authors.forename: David D
authors.initials: DD
authors.lastname: Frisbie
authors.forename: C Wayne
authors.initials: CW
authors.lastname: McIlwraith
authors.forename: Alan J
authors.initials: AJ
authors.lastname: Grodzinsky
mesh_terms: D000818:Animals; D001696:Biomechanical Phenomena; D002470:Cell Survival; D002478:Cells, Cultured; D020219:Chondrogenesis / Q000187:drug effects / Q000502:physiology*; D006736:Horses; D059630:Mesenchymal Stem Cells / Q000187:drug effects / Q000378:metabolism*; D011312:Pressure; D011509:Proteoglycans / Q000096:biosynthesis*; D013314:Stress, Mechanical; D023822:Tissue Engineering; D016212:Transforming Growth Factor beta / Q000494:pharmacology*
chemical_list: D011509:Proteoglycans; D016212:Transforming Growth Factor beta