Impact of High-Molecular-Weight Hyaluronic Acid on Gene Expression in Rabbit Achilles Tenocytes In Vitro

Int J Mol Sci. 2022 Jul 18;23(14):7926. doi: 10.3390/ijms23147926.

Abstract

(1) Background: Surgical tendon repair often leads to adhesion formation, leading to joint stiffness and a reduced range of motion. Tubular implants set around sutured tendons might help to reduce peritendinous adhesions. The lubricant hyaluronic acid (HA) is a viable option for optimizing such tubes with the goal of further enhancing the anti-adhesive effect. As the implant degrades over time and diffusion is presumed, the impact of HA on tendon cells is important to know. (2) Methods: A culture medium of rabbit Achilles tenocytes was supplemented with high-molecular-weight (HMW) HA and the growth curves of the cells were assessed. Additionally, after 3, 7 and 14 days, the gene expression of several markers was analyzed for matrix assembly, tendon differentiation, fibrosis, proliferation, matrix remodeling, pro-inflammation and resolution. (3) Results: The addition of HA decreased matrix marker genes, downregulated the fibrosis marker α-SMA for a short time and slightly increased the matrix-remodeling gene MMP-2. Of the pro-inflammatory marker genes, only IL-6 was significantly upregulated. IL-6 has to be kept in check, although IL-6 is also needed for a proper initial inflammation and efficient resolution. (4) Conclusions: The observed effects in vitro support the intended anti-adhesion effect and therefore, the use of HMW HA is promising as a biodegradable implant for tendon repair.

Keywords: IL-6; LPS; LipoxinA4; Mohawk; PAR-2; TNF-α; fibronectin; rabbit tenocytes; tenascin C; tenomodulin.

MeSH terms

  • Achilles Tendon* / metabolism
  • Animals
  • Gene Expression
  • Hyaluronic Acid / metabolism
  • Hyaluronic Acid / pharmacology
  • Inflammation / metabolism
  • Interleukin-6 / metabolism
  • Rabbits
  • Tenocytes* / metabolism
  • Tissue Adhesions

Substances

  • Interleukin-6
  • Hyaluronic Acid