title: Hylan G-F 20 attenuates posttraumatic osteoarthritis progression: Association with upregulated expression of the circardian gene NPAS2.
abstract: OBJECTIVE
  The study was to examine the effect of Hylan G-F 20 on the progression of posttraumatic osteoarthritis (PTOA) and the expression of the circadian genes neuronal PAS domain protein 2 (NPAS2) and period 2 (Per2).
  
  
  METHODS
  We used the anterior cruciate ligament transaction and medial menisectomy (ACLT+MMx) model in Wistar rats. The rats were divided into three groups, the sham-operated group, the Hylan G-F 20-treated group, and the saline-treated group. Rats which underwent ACLT + MMx surgery were injected intraarticularly with, respectively, Hylan G-F 20 or saline once a week for 3 consecutive weeks, starting 7days after surgery. The gross morphology and histopathology of the experimental knee joints were evaluated at the end of week 6. Expression of the NPAS2 and Per2 genes was measured by real-time PCR.
  
  
  RESULTS
  Hylan G-F 20 suppressed the articular cartilage destruction and synovitis compared to the saline-treated group. Compared to the sham-operated group, the Hylan G-F 20-treated group showed significantly upregulated expression of NPAS2 in cartilage (2.53±0.08-fold higher; p<0.05) and a non-significant increase in Per2 expression (2.35±1.26-fold higher p=0.28), while the saline-treated group showed significant downregulation of NPAS2 expression and a non-significant decrease in Per2 expression.
  
  
  CONCLUSIONS
  Our data suggested that early intraarticular injection of Hylan G-F 20 attenuates the progression of PTOA and significantly upregulates NPAS2 expression. These findings provide a new direction for studying associations between the use of a pharmacological agent, the degenerative process, and circadian gene expression.
authors.affiliation: Institute of Systems Biology and Bioinformatics, National Central University, Zhongli City, Taiwan; Department of Anesthesiology, Sijhih Cathay General Hospital, New Taipei City, Taiwan; Department of Anesthesiology, Taipei Medical University Hospital, Taipei, Taiwan.
authors.forename: Chih-Chung
authors.initials: CC
authors.lastname: Liu
authors.affiliation: Institute of Systems Biology and Bioinformatics, National Central University, Zhongli City, Taiwan.
authors.forename: Li-Jen
authors.initials: LJ
authors.lastname: Su
authors.affiliation: Department of Anesthesiology, Cathay General Hospital, Taipei, Taiwan.
authors.forename: Wei-Yuan
authors.initials: WY
authors.lastname: Tsai
authors.affiliation: Department of Anesthesiology, Sijhih Cathay General Hospital, New Taipei City, Taiwan; School of Medicine, Fu Jen Catholic University, New Taipei city, Taiwan.
authors.forename: Hsiao-Lun
authors.initials: HL
authors.lastname: Sun
authors.affiliation: Institute of Systems Biology and Bioinformatics, National Central University, Zhongli City, Taiwan; Department of Physics, Chung Yuan Christian University, Zhongli, Taiwan. Electronic address: hclee12345@gmail.com.
authors.forename: Hoong-Chien
authors.initials: HC
authors.lastname: Lee
authors.affiliation: Department of Anesthesiology, Cathay General Hospital, Taipei, Taiwan; Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan. Electronic address: w82556@gmail.com.
authors.forename: Chih-Shung
authors.initials: CS
authors.lastname: Wong
mesh_terms: D000818:Animals; D000070598:Anterior Cruciate Ligament Injuries; D051792:Basic Helix-Loop-Helix Proteins / Q000187:drug effects / Q000235:genetics*; D002940:Circadian Rhythm / Q000187:drug effects* / Q000235:genetics*; D018450:Disease Progression; D005552:Forelimb / Q000293:injuries; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D006820:Hyaluronic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D007270:Injections, Intra-Articular; D007596:Joints / Q000293:injuries; D009419:Nerve Tissue Proteins / Q000187:drug effects / Q000235:genetics*; D010003:Osteoarthritis / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D056950:Period Circadian Proteins / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D015854:Up-Regulation / Q000187:drug effects; D055675:Viscosupplements / Q000008:administration & dosage / Q000627:therapeutic use*; D014947:Wounds and Injuries / Q000150:complications*
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D006820:Hyaluronic Acid; D009419:Nerve Tissue Proteins; D056950:Period Circadian Proteins; D055675:Viscosupplements; C104264:NPAS2 protein, human; C513311:Per2 protein, rat; C049816:hylan
keywords: Arthritis; Circadian rhythm; Hyaluronic acid; Hylan; NPAS2