Osteogenic Protein-1 inhibits matrix depletion in a hyaluronan hexasaccharide-induced model of osteoarthritis

Abstract

Objective: To examine the capacity of recombinant osteogenic protein-1 (OP-1) to inhibit the cartilage extracellular matrix damage that follows treatment with hyaluronan hexasaccharides (HA6). Design: The effects of OP-1 were examined on isolated human chondrocytes grown in alginate beads as well as articular cartilage slices treated with hyaluronan hexasaccharides. Changes in the relative expression of messenger RNA for hyaluronan synthase- 2, aggrecan and CD44 were determined by competitive quantitative reverse transcriptase-polymerase chain reaction. Cartilage proteoglycan biosynthesis was examined by a 35S-sulfate incorporation assay. Cell-associated matrix of human chondrocytes was visualized by the use of particle exclusion assay, and alcian blue staining. Cartilage slices were examined for accumulation of proteoglycan by Safranin-O, and hyaluronan by a specific biotinylated probe. Results: Combined OP-1 and HA6 treatment resulted in enhanced expression of mRNA for aggrecan and HAS-2, compared to the treatment with HA6 only. This increased expression of aggrecan mRNA was paralleled by an increased synthesis of cartilage proteoglycan especially retained in the cell-associated matrix. Co-treatment with OP-1 inhibited the HA6-induced depletion of cell-associated matrices as well as HA6-induced depletion of hyaluronan and proteoglycan within cartilage tissue slices. Conclusions: These results demonstrate that OP-1 can abrogate the catabolic events associated with a HA6-induced matrix depletion model of osteoarthritis. The mRNA levels of two major cartilage extracellular matrix components, aggrecan and hyaluronan synthase-2 are enhanced above values obtained by either OP-1 or HA6 treatments alone.