title: A mechanical refractory period of chondrocytes after dynamic hydrostatic pressure.
abstract: OBJECTIVE
  Mechanical stimulation, a crucial factor for maintaining the cartilaginous phenotype and promoting the chondrogenesis, has been widely used in autologous chondrocyte transplantation. This study was designed to investigate a novel concept of mechanical refractory period of chondrocytes after dynamic hydrostatic pressure (dHP).
  
  
  METHODS
  dHP protocols (0.1 Hz, 2 MPa) were applied. The variation in type II collagen (Col II) expression induced by each dHP unit was measured. The dynamic remodeling of F-actin during the mechanical protocols was observed morphologically and mechanically by laser confocal microscopy and optical magnetic twisting cytometry (OMTC), respectively. About 20 ng/ml VEGF was used to stabilize the F-actin and restrain the mechanical refractory period.
  
  
  RESULTS
  Compared with the remarkable increase of Col II (16-fold) induced by the initial dHP unit, the chondrocytes entered a mechanical refractory period and the second unit hardly elevated Col II expression (only 2.9-fold). This refractory period recovered partially within 2 h. The uniform, parallel, and coarse fibers of F-actin before dHP became thin, sparse, and disordered, and the cell stiffness decreased concomitantly. The variations in both the morphology and the mechanical property of F-actin were highly synchronous to the mechanical refractory period and recovered in a time-dependent manner. VEGF postponed the appearance of this refractory period and maintained the high expression of Col II by VEGF/p38/MAPKAPK-2/LIMK/cofilin pathway.
  
  
  CONCLUSIONS
  A mechanical refractory period of chondrocytes has been discovered and defined in this study. The F-actin depolymerization is the putative mechanism, and this refractory period can be postponed by VEGF-induced F-actin stabilization.
authors.affiliation: Department of Orthopedics and.
authors.forename: Xu
authors.initials: X
authors.lastname: Cao
authors.forename: Hansong
authors.initials: H
authors.lastname: Xia
authors.forename: Na
authors.initials: N
authors.lastname: Li
authors.forename: Kun
authors.initials: K
authors.lastname: Xiong
authors.forename: Zili
authors.initials: Z
authors.lastname: Wang
authors.forename: Song
authors.initials: S
authors.lastname: Wu
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism*; D000818:Animals; D002356:Cartilage / Q000378:metabolism*; D002454:Cell Differentiation / Q000502:physiology; D002478:Cells, Cultured; D019902:Chondrocytes / Q000166:cytology*; D024043:Collagen Type II / Q000378:metabolism; D006874:Hydrostatic Pressure; D011817:Rabbits; D013314:Stress, Mechanical
chemical_list: D024043:Collagen Type II
keywords: Chondrocyte; F-actin remodeling; VEGF; cofilin; mechanical refractory period