title: Dynamic compression improves biosynthesis of human zonal chondrocytes from osteoarthritis patients.
abstract: OBJECTIVE
  We hypothesize that chondrocytes from distinct zones of articular cartilage respond differently to compressive loading, and that zonal chondrocytes from osteoarthritis (OA) patients can benefit from optimized compressive stimulation. Therefore, we aimed to determine the transcriptional response of superficial (S) and middle/deep (MD) zone chondrocytes to varying dynamic compressive strain and loading duration. To confirm effects of compressive stimulation on overall matrix production, we subjected zonal chondrocytes to compression for 2 weeks.
  
  
  METHODS
  Human S and MD chondrocytes from osteoarthritic joints were encapsulated in 2% alginate, pre-cultured, and subjected to compression with varying dynamic strain (5, 15, 50% at 1 Hz) and loading duration (1, 3, 12 h). Temporal changes in cartilage-specific, zonal, and dedifferentiation genes following compression were evaluated using quantitative real-time reverse transcriptase polymerase chain reaction (qRT-PCR). The benefits of long-term compression (50% strain, 3 h/day, for 2 weeks) were assessed by measuring construct glycosaminoglycan (GAG) content and compressive moduli, as well as immunostaining.
  
  
  RESULTS
  Compressive stimulation significantly induced aggrecan (ACAN), COL2A1, COL1A1, proteoglycan 4 (PRG4), and COL10A1 gene expression after 2 h of unloading, in a zone-dependent manner (P < 0.05). ACAN and PRG4 mRNA levels depended on strain and load duration, with 50% and 3 h loading resulting in highest levels (P < 0.05). Long-term compression increased collagen type II and ACAN immunostaining and total GAG (P < 0.05), but only S constructs showed more PRG4 stain, retained more GAG (P < 0.01), and developed higher compressive moduli than non-loaded controls.
  
  
  CONCLUSIONS
  The biosynthetic activity of zonal chondrocytes from osteoarthritis joints can be enhanced with selected compression regimes, indicating the potential for cartilage tissue engineering applications.
authors.affiliation: Institute of Health and Biomedical Innovation, Queensland University of Technology, 60 Musk Ave., Kelvin Grove, QLD 4059, Australia. juokchun@gmail.com
authors.forename: J E
authors.initials: JE
authors.lastname: Jeon
authors.forename: K
authors.initials: K
authors.lastname: Schrobback
authors.forename: D W
authors.initials: DW
authors.lastname: Hutmacher
authors.forename: T J
authors.initials: TJ
authors.lastname: Klein
mesh_terms: D000368:Aged; D053674:Aggrecans / Q000096:biosynthesis / Q000235:genetics; D002358:Cartilage, Articular / Q000378:metabolism*; D019902:Chondrocytes / Q000378:metabolism*; D003094:Collagen / Q000096:biosynthesis / Q000235:genetics; D019245:Compressive Strength; D006025:Glycosaminoglycans / Q000378:metabolism; D006801:Humans; D008875:Middle Aged; D020370:Osteoarthritis, Knee / Q000235:genetics / Q000378:metabolism*; D011509:Proteoglycans / Q000096:biosynthesis / Q000235:genetics; D013314:Stress, Mechanical; D013997:Time Factors
chemical_list: D053674:Aggrecans; D006025:Glycosaminoglycans; D011509:Proteoglycans; D003094:Collagen