title: Biomechanical signals exert sustained attenuation of proinflammatory gene induction in articular chondrocytes.
abstract: OBJECTIVE
  Physical therapies are commonly used for limiting joint inflammation. To gain insight into their mechanisms of actions for optimal usage, we examined persistence of mechanical signals generated by cyclic tensile strain (CTS) in chondrocytes, in vitro. We hypothesized that mechanical signals induce anti-inflammatory and anabolic responses that are sustained over extended periods.
  
  
  METHODS
  Articular chondrocytes obtained from rats were subjected to CTS for various time intervals followed by a period of rest, in the presence of interleukin-1beta (IL-1beta). The induction for cyclooxygenase (COX-2), inducible nitric oxide synthase (iNOS), matrix metalloproteinase (MMP)-9, MMP-13 and aggrecan was analyzed by real-time polymerase chain reaction (PCR), Western blot analysis and immunofluorescence.
  
  
  RESULTS
  Exposure of chondrocytes to constant CTS (3% CTS at 0.25 Hz) for 4-24 h blocked more than 90% (P<0.05) of the IL-1beta-induced transcriptional activation of proinflammatory genes, like iNOS, COX-2, MMP-9 and MMP-13, and abrogated inhibition of aggrecan synthesis. CTS exposure for 4, 8, 12, 16, or 20 h followed by a rest for 20, 16, 12, 8 or 4h, respectively, revealed that 8h of CTS optimally blocked (P<0.05) IL-1beta-induced proinflammatory gene induction for ensuing 16 h. However, CTS for 8h was not sufficient to inhibit iNOS expression for ensuing 28 or 40 h.
  
  
  CONCLUSIONS
  Data suggest that constant application of CTS blocks IL-1beta-induced proinflammatory genes at transcriptional level. The signals generated by CTS are sustained after its removal, and their persistence depends upon the length of CTS exposure. Furthermore, the sustained effects of mechanical signals are also reflected in their ability to induce aggrecan synthesis. These findings, once extrapolated to human chondrocytes, may provide insight in obtaining optimal sustained effects of physical therapies in the management of arthritic joints.
authors.affiliation: Department of Oral Biology, The Ohio State University, Columbus, OH 43210, USA.
authors.forename: S
authors.initials: S
authors.lastname: Madhavan
authors.forename: M
authors.initials: M
authors.lastname: Anghelina
authors.forename: B
authors.initials: B
authors.lastname: Rath-Deschner
authors.forename: E
authors.initials: E
authors.lastname: Wypasek
authors.forename: A
authors.initials: A
authors.lastname: John
authors.forename: J
authors.initials: J
authors.lastname: Deschner
authors.forename: N
authors.initials: N
authors.lastname: Piesco
authors.forename: S
authors.initials: S
authors.lastname: Agarwal
mesh_terms: D053674:Aggrecans / Q000096:biosynthesis*; D000818:Animals; D002358:Cartilage, Articular / Q000378:metabolism*; D019902:Chondrocytes / Q000378:metabolism*; D053583:Interleukin-1beta / Q000494:pharmacology; D020782:Matrix Metalloproteinases / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000096:biosynthesis*; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D051381:Rats; D013314:Stress, Mechanical
chemical_list: D053674:Aggrecans; D053583:Interleukin-1beta; D019001:Nitric Oxide Synthase; D011451:Prostaglandin-Endoperoxide Synthases; D020782:Matrix Metalloproteinases