Hyaluronan (or hyaluronic acid, @entity15773 ) is an essential component of extracellular matrices. It interacts with other macromolecules and plays a predominant role in tissue morphogenesis, cell migration, differentiation, and adhesion. The cell signaling functions of @entity15773 are mediated through the CD-44 receptor and are dependent upon the molecular weight of the polymer. We hypothesized that an @entity15773 of appropriate molecular weight alone in optimal concentration may induce osteoblast differentiation and bone formation. Enzyme-digested calvarial-derived mesenchymal cells from 2-day-old newborn @entity35 were cultured with the addition of @entity15773 of three different molecular weights (2300, 900, and 60 kDa). We added, 0.5, 1.0, and 2.0 mg/mL @entity15773 for each molecular weight to the medium at the first plating of cells. After 7 to 20 days in culture, cell proliferation and differentiation were evaluated by measuring @entity1014 incorporation, alkaline phosphatase activity, and @entity9356 gene expression. The effects of @entity15773 on bone formation were examined by using @entity622 staining for mineralization. The results showed that low molecular weight @entity15773 (60 kDa) significantly stimulated cell growth, increased @entity9356 mRNA expression in a dose-dependent manner, but showed no apparent effects on alkaline phosphatase activity and bone mineralization. On the other hand, high-weight @entity15773 (900 and 2,300 kDa) significantly increased all the parameters examined, particularly alkaline phosphatase activity, in a dose-dependent manner and stimulated cell mineralization to 126% and 119% of the controls, respectively, in the 1.0 mg/mL dose. Our findings suggest that @entity15773 has a molecular weight-specific and dose-specific mode of action that may enhance the osteogenic and osteoinductive properties of bone graft materials and substitutes due to its stimulatory effects on osteoblasts.

The effect of hyaluronan on osteoblast proliferation and differentiation in XXXX calvarial-derived cell cultures.

@entity15773 :: ('MESH:C537629', 'Disease') :: ['HA'] @entity622 :: ('MESH:C010078', 'Chemical') :: ['Alizarin red'] @entity9356 :: ('81613(Tax:10116)', 'Gene') :: ['osteocalcin'] @entity1014 :: ('MESH:D013936', 'Chemical') :: ['thymidine'] @entity35 :: ('10116', 'Species') :: ['rats']
@entity35 :: (10116,Species) :: ['rat']
