Development of antisense oligonucleotide (ASO) technology against Tgf-β signaling to prevent scarring during flexor tendon repair

Autor: Sirish Kondabolu, Regis J. O'Keefe, Alayna E. Loiselle, Shanshan Shi, Hani A. Awad, Jennifer H. Jonason, Michael B. Geary, Kiminori Yukata
Rok vydání: 2015
Předmět:
Zdroj: Journal of Orthopaedic Research. 33:859-866
ISSN: 0736-0266
DOI: 10.1002/jor.22890
Popis: Flexor tendons (FT) in the hand provide near frictionless gliding to facilitate hand function. Upon injury and surgical repair, satisfactory healing is hampered by fibrous adhesions between the tendon and synovial sheath. In the present study we used antisense oligonucleotides (ASOs), specifically targeted to components of Tgf-β signaling, including Tgf-β1, Smad3 and Ctgf, to test the hypothesis that local delivery of ASOs and suppression of Tgf-β1 signaling would enhance murine FT healing by suppressing adhesion formation while maintaining strength. ASOs were injected in to the FT repair site at 2, 6 and 12 days post-surgery. ASO treatment suppressed target gene expression through 21 days. Treatment with Tgf-β1, Smad3 or Ctgf ASOs resulted in significant improvement in tendon gliding function at 14 and 21 days, relative to control. Consistent with a decrease in adhesions, Col3a1 expression was significantly decreased in Tgf-β1, Smad3 and Ctgf ASO treated tendons relative to control. Smad3 ASO treatment enhanced the maximum load at failure of healing tendons at 14 days, relative to control. Taken together, these data support the use of ASO treatment to improve FT repair, and suggest that modulation of the Tgf-β1 signaling pathway can reduce adhesions while maintaining the strength of the repair.
Databáze: OpenAIRE
Externí odkaz: