Exploring a role for biglycan in regulating the regenerative potential of mesenchymal stem cells in bone repair

Objectives: To investigate how the BGN expression correlates to the regenerative capacity of the MSC population.
Methods: Heterogeneous MSC populations, isolated from femoral compact bone of 28 day old male Wistar rats, were culture expanded monitoring expression of MSC and cell senescent markers. At PD15 and 50 temporal expression of cell proliferation marker, Ki-67, matrix proteins, BGN and Col1a1 and BGN cell internalisation receptor, HARE were quantified by qPCR and Western blot analysis during osteogenic differentiation. Mineral deposition was identified by alizarin red staining.
Results: Extensive characterisation identified MSC populations with differing heterogeneous profile. PD15 cells likely contained predominately lineage-restricted cells with low proliferative capacity and high osteogenic potential. At PD50 these cells appear to be lost to leave immature transit amplifying MSCs of higher proliferative capacity and take longer to synthesise a mineralised matrix. During osteogenic stimulation, cell populations responded differently. Compared with PD15 cells, expression of ki-67 in PD50 cells was initially reduced in osteogenic media, which correlated with a delay in mineral deposition. No difference in BGN or Col1a gene expression was observed between the MSC populations, however, HARE was initially reduced in PD50 populations, possibly correlating with the prolonged presence of BGN protein within the extracellular matrix.
Conclusions: The results of this study support previous purported evidence suggesting a role for BGN in stimulating early osteogenic differentiation, which may be of value in enhancing bone tissue engineering approaches in dentistry.