Conclusions
These findings provide the basis for future studies to elucidate the signaling mechanisms responsible for osteoblast matrix-mediated regulation of MSC osteogenesis and to better manipulate MSC fate in vitro to minimize their spontaneous differentiation.
Methods
We examined here how osteogenic differentiation of MSCs in vitro is affected by exposure to osteoblastic cells (OBCs). Human bone marrow MSCs were exposed to OBCs, derived by induced osteogenic differentiation of MSCs, either directly in contact co-cultures, or indirectly to OBC-conditioned medium or decellularized OBC extracellular matrix (ECM).
Results
Our results showed that OBCs can act as negative regulators of MSC osteogenesis. mRNA expression profiling revealed that OBCs did not affect MSC osteogenesis in direct contact cultures or via secreted factors. However, seeding MSCs on decellularized OBC ECM significantly decreased expression of several osteogenic genes and maintained their fibroblastic morphologies. Proteomic analysis identified some of the candidate protein regulators of MSC osteogenesis. Conclusions: These findings provide the basis for future studies to elucidate the signaling mechanisms responsible for osteoblast matrix-mediated regulation of MSC osteogenesis and to better manipulate MSC fate in vitro to minimize their spontaneous differentiation.