Osteogenic protein 1 stimulates cell-associated matrix assembly by normal human articular chondrocytes: Up-regulation of hyaluronan synthase, CD44, and aggrecan

Abstract

Objective To determine the effects of osteogenic protein 1 (OP‐1) on hyaluronan (HA), CD44, and aggrecan biosynthesis as well as the contribution of these molecules in promoting matrix assembly by human articular chondrocytes. Methods Normal human chondrocytes were cultured with or without OP‐1 treatment. Changes in the relative expression of messenger RNA (mRNA) for HA synthases 2 and 3 (HAS‐2 and HAS‐3), CD44, and aggrecan were determined by competitive quantitative reverse transcriptase–polymerase chain reaction. Accumulation of HA was characterized by indirect staining, CD44 by flow cytometry, and aggrecan biosynthesis by ³⁵SO₄ incorporation. Results OP‐1 stimulated the expression of HAS‐2, CD44, and aggrecan mRNA in a time‐dependent manner, resulting in increased expression of HA, CD44, and aggrecan. Prominent increases in HA‐rich cell‐associated matrices were also observed. Conclusion OP‐1 stimulates not only the synthesis of matrix macromolecules such as aggrecan, but also the synthesis of other molecules required for matrix retention, namely, HA and CD44.