ABSTRACT
The effect of S-adenosyl-L-methionine (SAMe) on human articular osteoarthritic chondrocytes was studied using a thick-layer culture model. Three SAMe concentrations were tested (1, 10, and 100 micrograms/ml). For 10 micrograms/ml, the most efficient dose, a significant rise in the incorporation levels of 35S-sulfate and 3H-serine was observed, as was as an increase in the hexuronic acid content. All the parameters seem to express a more active protein synthesis, particularly for proteoglycans. Under the same conditions, the proliferation rate of chondrocytes does not undergo important variations. These results point to a direct action on the cell metabolism but little is known concerning the mechanism involved.
Subject(s)
Cartilage, Articular/drug effects , S-Adenosylmethionine/pharmacology , Cartilage, Articular/cytology , Cartilage, Articular/metabolism , Cells, Cultured/drug effects , Dose-Response Relationship, Drug , Hexuronic Acids/metabolism , Humans , Proteoglycans/biosynthesis , S-Adenosylmethionine/administration & dosage , Serine/metabolism , Sulfates/metabolismSubject(s)
Disease Models, Animal , Knee Joint , Osteoarthritis/etiology , Animals , Male , Pressure , RabbitsABSTRACT
Chondrocytes derived by outgrowth from normal and osteoarthrotic human femoral head cartilage were grown in high density cultures for five passages. Cultures were analysed for their sulfated macromolecular components in medium, layer-matrix and intracellular compartments. Two fractions were obtained: typical proteoglycans and glycosaminoglycan-peptides (Mr approx. 60 000) which might result from an enzymatic degradation of proteoglycans. Proteoglycans from normal and osteoarthrotic cultures exhibited similar biochemical properties (size, protein:uronic acid ratio, glycosaminoglycan composition). Slightly less proteoglycans were aggregated with hyaluronic acid in osteoarthrotic than in normal cultures. Three populations of proteoglycan subunit were obtained under dissociative conditions (Sepharose CL-2B) in both normal and osteoarthrotic cultures: proteoglycan 1 (Kav=0.04), proteoglycan 2 (Kav=0.26) which were aggregated with hyaluronic acid in associative conditions, and proteoglycan 4 (Kav=0.48). A fourth population, proteoglycan 3 (Kav=0.33, Sepharose 2B and CL-2B) was intracellular in osteoarthrotic cultures. After a 4 day incubation period, about 60% more proteoglycans were found in osteoarthrotic than in normal cultures (medium+52%, layer-matrix + 44% and 17 times the normal value inside the cells). Proteoglycan distribution kinetics in the three compartments showed a higher net accumulation of proteoglycans in osteoarthrotic-derived cultures.
