EN
Human mesenchymal stem cells (hMSCs) have
been demonstrated to exhibit characteristic cytosolic Ca2+ ([Ca2+]i) oscillations in response to physicochemical factors,
including soluble factors, matrix proteins and microenvironment.
It has been postulated that the calcium
oscillation at the early stages of hMSC differentiation may
serve as a biophysical predictor. The goal of the present
study is therefore aimed at elucidating the matrix proteinmediated
[Ca2+]i oscillation that occurs in the early stages
of hMSC osteogenic differentiation. On the collagen substrates
of different stiffness and concentrations, intracellular
[Ca2+]i oscillations of hMSCs exhibited rapid spikes
on the hard substrates and the opposite on the soft substrate.
Cells seeded on a hard substrate also expressed signi
ficantly high levels of osteogenic gene markers, suggesting
a key role of intracellular calcium in the transduction
of ECM signaling to the hMSC differentiation. Our findings
revealed that the characteristics of [Ca2+]i oscillation
are regulated by the biochemical and mechanical properties
of the collagen substrate. Furthermore, β1-integrin
and associated signaling proteins found in focal adhesions
(FAs) were involved in the signaling pathways. Because
the [Ca2+]i signaling and stemcell differentiation appear
closely correlated, the regulation of [Ca2+]i signaling
through the modification of engineeredECMmay provide a
controllable exogenous technique to direct the fate of hMSCs.