Hyaluronic Acid Modulates Cell Proliferation Unequally in Intrasynovial and Extrasynovial Rabbit Tendons In Vitro

Abstract

As tendons differ in biochemical composition and cellular capacities, we have compared dose response effects of hyaluronic acid on cell proliferation and synthesis of matrix components in intermediate and proximal segments of intrasynovial deep flexor tendons and extrasynovial peroneus rabbit tendons in vitro. Compared with matched control tendons, hyaluronic acid inhibited cell proliferation in intermediate and proximal intrasynovial flexor tendon segments at the concentrations of 0.1-2.0 mg/ml and 0.5-2.0 mg/ml respectively, but in extrasynovial tendon segments only at the concentration of 0.5 mg/ml. Hyaluronic acid did not affect synthesis of proteoglycan, collagen and non-collagen protein in either type of tendon. These results show that hyaluronic acid modulates cell proliferation unequally in intra- and extrasynovial tendons without affecting the synthesis of matrix components in the two types of tendons, indicating differential hyaluronic acid sensitivity and a possible mechanism of action.

The Inflammatory Response and Hyaluronan Synthases in the Rabbit Flexor Tendon and Tendon Sheath Following Injury

“…In clinical trials, attempts have been made to decrease adhesion formation after acute flexor tendon injury through treatment with exogenous HA. Although a number of animal studies have shown a capacity for HA to reduce adhesion formation, the clinical trials performed thus far could not demonstrate a significant improvement in outcomes after HA treatment (Hagberg, 1992;Moro-oka et al, 2000;Ö zgenel, 2004;Wiig and Abrahamsson, 2000). Possible explanations for such failures include the concentration of HA used in the studies, the half-life of the HA, and the mode of delivery.…”

Hyaluronic acid of high molecular weight inhibits proliferation and induces cell death in U937 macrophage cells

“…At concentrations ranging from 50 Ag/mL to 1 mg/mL, high molecular weight HA has been reported to stimulate proliferation of chondrocytes (Kawasaki et al, 1999), mesothelial cells (Reijnen et al, 2000), fibroblasts (Yoneda et al, 1988), cornea (Inoue and Katakami, 1993), melanoma (Ahrens et al, 2001), and mesangial cells (Mahadevan et al, 1991). Other reports have shown that high molecular weight HA inhibits proliferation of fibroblasts (Cortivo et al, 1990;Mast et al, 1991), chondroblasts (Cortivo et al, 1990), synovial (Goldberg and Toole, 1987), ovary (Dübe et al, 2001), endothelial (Sattar et al, 1992), and flexor tendon cells (Wiig and Abrahamsson, 2000). High molecular weight HA also has been shown to decrease chondrocyte apoptosis induced by anti-Fas antibody (Lisignoli et al, 2001) or following experimental induction of osteoarthritis (Takahashi et al, 2000).…”

Ultrasound-guided percutaneous injection to treat de Quervain’s disease using three different techniques: a randomized controlled trial

“…In addition, low molecular weight HA has been reported to have a mild antinociceptive effect in the synovial space [23]. Furthermore, experimental studies showed that HA has a direct effect on tendons by inhibiting and modulating fibroblast activity that is impaired when stenosing tenosynovitis is present [23][24][25]. These data are the basis of the rationale of our study.…”