Chondrocytes Are Regulated by Cellular Adhesion Through CD44 and Hyaluronic Acid Pathway

TLDR

Articular cartilage contains chondrocytes embedded in an extracellular matrix rich in collagen and hyaluronic acid, and although CD44 is a key HA receptor in cartilage, it is unclear whether chondrocytes adhere to HA through CD44 or how such adhesion influences chondrocyte function. The study investigates how CD44 mediates chondrocyte adhesion to hyaluronic acid and the resulting effects on chondrocyte function. The authors used the HCS‑2/8 human chondrosarcoma‑derived chondrocyte‑like cell line to examine CD44‑dependent adhesion to hyaluronic acid. HCS‑2/8 cells express CD44, adhere to hyaluronic acid via CD44, and this adhesion stimulates proliferation, c‑myc, and TGF‑β mRNA expression, all of which are blocked by CD44‑blocking antibodies.

Abstract

Abstract The articular cartilage consists of resident chondrocytes embedded within the extracellular matrix which contains several components such as collagen and hyaluronic acids (HA). CD44 is a major cell surface receptor for HA and is homologous to cartilage-link proteins. Although CD44 is present in cartilage, it is not clear if chondrocytes adhere to HA through CD44 or whether such adhesion changes the function of chondrocytes. We studied the molecular mechanisms of CD44-related chondrocyte adhesion to HA and the effects of such adhesion on chondrocyte function. Experiments were performed using the human chondrosarcoma-derived chondrocyte-like cell line HCS-2/8. Our results showed that (a) HCS-2/8 cells highly expressed CD44; (b) HCS-2/8 cells efficiently adhered to HA without any stimuli; (c) monoclonal antibody (mAb)-blocking studies indicated that adhesion of HCS-2/8 cells to HA was mainly mediated by the CD44/HA pathway; (d) cellular adhesion to HA increased the proliferation of HCS-2/8 cells, independent of transforming growth factor-β (TGF-β), but this was inhibited by CD44 mAb; (e) the adhesion of chondrocytes to HA also induced c-myc mRNA expression and this was also inhibited by CD44 mAb; and (f) the adhesion of cells to HA augmented TGF-β mRNA expression, a process also reduced by CD44 mAb. Thus, HCS-2/8 cells effectively adhered to HA through cell surface CD44. The adhesion was also involved in cellular signaling which induced cellular proliferation and expression of c-myc mRNA as well as TGF-β mRNA expression within the cells. Our results indicate that CD44 on chondrocytes plays an important role in normal and abnormal functions of cartilage through its adhesion to HA, which induces a variety of stimulatory signals to regulate chondrocyte proliferation as well as matrix synthesis in cartilage microenvironment.