Positive Regulation of S-Adenosylmethionine on Chondrocytic Differentiation via Stimulation of Polyamine Production and the Gene Expression of Chondrogenic Differentiation Factors

Hoang LD, Aoyama E, Hiasa M, Omote H, Kubota S, Kuboki T · International Journal of Molecular Sciences

Reproduces the 1987 proteoglycan finding and supplies the mechanism it lacked. Aggrecan accumulation rose 10.6 percent at day 7 and 31.3 percent at day 14 by Alcian blue absorbance, while cell proliferation did not rise at all and fell at the most effective concentration, so the extra matrix is per-cell output rather than more cells. Gene expression of aggrecan, type II collagen, SOX9, CCN2 and chondroitin sulfate biosynthetic enzymes rose. Blocking intracellular SAM synthesis with a MAT2A inhibitor, and again by knocking MAT2A down, lowered aggrecan, type II collagen and CHSY1 expression, and exogenous SAM reversed it. Polyamine levels rose in treated cells, and inhibiting polyamine synthesis removed most of the effect on aggrecan, which is what identifies the route.

Population

HCS-2/8 human chondrocyte-like cells, with confirmatory work in a rat chondrosarcoma cell line

Intervention

Exogenous S-adenosylmethionine, most effectively at 10 micrograms per millilitre

Comparator

Untreated culture, plus MAT2A inhibition and knockdown to test the pathway from the other direction

Limitations

A cell line rather than primary human osteoarthritic chondrocytes, and a chondrosarcoma-derived one, so it models a chondrocyte phenotype rather than diseased cartilage. Culture concentrations bear no established relationship to what an oral dose delivers to a joint. No animal and no person in it.