Heparin affects XXXX bone marrow stromal cell fate: Promoting osteogenic and reducing adipogenic differentiation and conversion.

@entity1 @entity13062 @entity170 @entity14539 @entity887 @entity5741 @entity715 @entity623 @entity6861
UNASSIGNED: Heparins are broadly used for the prevention and treatment of @entity715 and @entity887 . Yet, @entity170 is considered to be a severe side effect in up to one third of all @entity1 on long-term treatment. However, the mechanisms underlying this clinical problem are only partially understood. To investigate if heparin affects differentiation of skeletal precursors, we examined the effects of heparin on the osteogenic and adipogenic lineage commitment and differentiation of primary @entity1 bone marrow stromal cells (hBMSCs). Due to the known inverse relationship between adipogenesis and osteogenesis and the capacity of pre-differentiated cells to convert into the respective other lineage, we also determined heparin effects on osteogenic conversion and adipogenic differentiation/conversion. Interestingly, heparin did not only significantly increase mRNA expression and enzyme activity of the osteogenic marker @entity623 ( @entity623 ), but it also promoted mineralization during osteogenic differentiation and conversion. Furthermore, the mRNA expression of the osteogenic marker @entity13062 ( @entity13062 ) was enhanced. In addition, heparin administration partly prevented adipogenic differentiation and conversion demonstrated by reduced lipid droplet formation along with a decreased expression of adipogenic markers. Moreover, luciferase reporter assays, inhibitor experiments and gene expression analyses revealed that heparin had putative permissive effects on osteogenic signaling via the @entity6861 pathway and reduced the mRNA expression of the Wnt pathway inhibitors @entity5741 ( @entity5741 ) and sclerostin ( @entity14539 ). Taken together, our data show a rather supportive than inhibitory effect of heparin on osteogenic hBMSC differentiation and conversion in vitro. Further studies will have to investigate the net effects of heparin administration on bone formation versus bone resorption in vivo to unravel the molecular mechanisms of heparin-associated @entity170 and reconcile conflicting experimental data with clinical observations.
