Studies have been conducted to highlight the anti-inflammatory and immunosuppressive
properties of cannabinoids and also their potentials for cartilage repair and regeneration.
Various wound healing techniques can be used to investigate the mechanisms of
chondrocyte repair in monolayers or three dimensional tissue constructs. The effect of
different concentrations of the synthetic cannabinoids WIN55, 212-2 (WIN-2), URB602
and HU-308 with and without their antagonists on the wound healing of chondrocyte
monolayers was investigated using a simple scratch assay model. The three
cannabinoids were found to increase wound healing of chondrocyte monolayers, but at
different rates. WIN55, 212-2 at a concentration of 1μM had the highest effect of
increasing both migration and proliferation of chondrocytes cultured in a chondrogenic
media, which increased the rate of wound closure. It was also found that treating the
cells with 2μM of any of the cannabinoids lead to a decrease in cell proliferation and the
rate of wound closure. These findings were further investigated, by studying the effect
of WIN-2 on nitric oxide (NO) and matrix metalloproteinase-2 (MMP-2) expressed by
wounded chondrocyte monolayers. Moreover, expression of collagen type-I, collagen
type-II, fibronectin and S100 proteins were detected using immunofluorescence and
verified quantitatively using ELISA based techniques, following treatment with 1μM
and 2μM of WIN-2, for both 2D monolayers and 3D sheets. Treating chondrocytes with
1μM of WIN-2 significantly increased collagen type-II, fibronectin and S100, and
significantly reduced collagen type-I compared to control groups in monolayers and
chondrocyte cell sheets. On the other hand, both concentrations of WIN-2 significantly
reduced the expression of the inflammation markers NO, and MMP-2, in a dose
dependent manner. These findings highlight the potential use of the synthetic
cannabinoid for improving the rate of wound closure as well as acting as an antiinflammatory
agent, which could be used to enhance tissue engineering protocols aimed
at cartilage repair.
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