title: Chitosan prevents adhesion during rabbit flexor tendon repair via the sirtuin 1 signaling pathway.
abstract: Chitosan has been demonstrated to exert potent anti-adhesive activity during tendon repair; however, the underlying molecular mechanisms remain unclear. The present study aimed to investigate the preventive effects of chitosan on adhesion in rabbit tendon repair, and to investigate the role of the sirtuin (SIRT)1 signaling pathway in this process. A total of 30 rabbits were divided randomly into three equal groups: Group 1, saline treatment; group 2, chitosan treatment; and group 3, chitosan + nicotinamide treatment. The flexor tendon of each of the rabbits was injured, and subsequently each rabbit was injected with the one of the reagents. Six weeks post‑surgery, all of the rabbits were sacrificed and their flexor tendons were harvested for subsequent evaluation of adhesion. Western blotting was used to determine the protein expression levels of specific signaling molecules. An MTT assay was conducted to evaluate the viability of human tenocytes and flow cytometry was used to analyze the apoptotic rate of the cells. The present study demonstrated that treatment with chitosan relieved adhesion in the rabbits with flexor tendon injuries. In addition, chitosan treatment increased SIRT1 expression, and reduced acetylated p65 and p53 expression in the tendons. The effects of chitosan on the tendons were attenuated by treatment with nicotinamide (a SIRT1 inhibitor). In the human tenocytes, pretreatment with chitosan resulted in an inhibition of interleukin (IL)‑1β‑induced apoptosis. Furthermore, chitosan reversed the IL‑1β‑induced downregulation of SIRT1 and upregulation of acetylated p65 and p53. Furthermore, downregulation of Sirt1 by RNA interference abrogated the effects of chitosan on the levels of p65 and p53 acetylation, and the rate of tenocyte apoptosis. In conclusion, chitosan treatment prevented adhesion via the SIRT1 signaling pathway during rabbit flexor tendon repair. These results indicate that SIRT1 may be targeted for therapeutic intervention in flexor tendon injury.
authors.affiliation: Department of Hand Surgery, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, P.R. China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Chen
authors.affiliation: Department of Hand Surgery, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, P.R. China.
authors.forename: Hui
authors.initials: H
authors.lastname: Lu
authors.affiliation: Department of Hand Surgery, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, P.R. China.
authors.forename: Hu
authors.initials: H
authors.lastname: Yang
mesh_terms: D000107:Acetylation / Q000187:drug effects; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D048271:Chitosan / Q000494:pharmacology*; D004195:Disease Models, Animal; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D005786:Gene Expression Regulation; D006801:Humans; D053583:Interleukin-1beta / Q000494:pharmacology; D008297:Male; D009536:Niacinamide / Q000494:pharmacology; D061251:Primary Cell Culture; D011817:Rabbits; D015398:Signal Transduction / Q000187:drug effects*; D056564:Sirtuin 1 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D013708:Tendon Injuries / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D013710:Tendons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D000267:Tissue Adhesions / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism; D014945:Wound Healing / Q000187:drug effects / Q000502:physiology; D019892:eIF-2 Kinase / Q000235:genetics / Q000378:metabolism
chemical_list: D053583:Interleukin-1beta; D016159:Tumor Suppressor Protein p53; D009536:Niacinamide; D048271:Chitosan; D019892:eIF-2 Kinase; D056564:Sirtuin 1