Hyaluronan inhibits BMP-induced osteoblast differentiation

FEBS Lett. 2015 Feb 13;589(4):447-54. doi: 10.1016/j.febslet.2014.12.031. Epub 2015 Jan 12.

Abstract

Hyaluronan (HA), one of the major structural extracellular components in cartilage, regulates cellular responses via receptors such as CD44. However, the direct effects of HA on osteoblastic differentiation has not been studied in detail. Here, we investigated the effects of HA (molecular weight: 900-1200 kDa) on osteoblastic differentiation that was induced by bone morphogenetic protein (BMP) in C2C12 cells (mouse myoblastic cells) and ST2 cells (mouse bone marrow cells). BMP-induced osteoblastic differentiation and Smad1/Smad5/Smad8 phosphorylation were downregulated by HA. Use of the CD44-blocking antibody restored HA-induced inhibition of osteoblastic differentiation and Smad1/Smad5/Smad8 phosphorylation. Our results indicate that HA inhibits BMP-induced osteoblastic differentiation through the CD44 receptor.

Keywords: Bone morphogenetic protein; CD44; Hyaluronan; Osteoblast.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Alkaline Phosphatase / metabolism
  • Animals
  • Bone Morphogenetic Protein 2 / physiology*
  • Cell Differentiation*
  • Cell Line
  • Female
  • Humans
  • Hyaluronan Receptors / metabolism
  • Hyaluronic Acid / pharmacology*
  • Hyaluronic Acid / physiology
  • Male
  • Mice
  • Middle Aged
  • Osteoarthritis / metabolism
  • Osteoarthritis / pathology
  • Osteoblasts / physiology*
  • Restriction Mapping
  • rho GTP-Binding Proteins / metabolism
  • rhoA GTP-Binding Protein

Substances

  • BMP2 protein, human
  • Bone Morphogenetic Protein 2
  • Cd44 protein, mouse
  • Hyaluronan Receptors
  • Hyaluronic Acid
  • Alkaline Phosphatase
  • RhoA protein, mouse
  • rho GTP-Binding Proteins
  • rhoA GTP-Binding Protein