Conclusions
Therefore, ciliotherapies can be utilised to enhance MSC ciliogenesis resulting in enhanced mechanosensitivity, however, only fenoldopam is a viable ciliotherapeutic option to enhance MSC osteogenesis.
Methods
MSCs were treated with forskolin, lithium chloride (LiCl) or fenoldopam to investigate the effect on ciliogenesis and cilia-associated signalling. Moreover, both early and long term biochemical and biophysical (fluid shear) induced osteogenic differentiation was examined in terms of osteogenic gene expression and bone matrix deposition following each treatment.
Results
LiCl and fenoldopam were found to enhance MSC ciliogenesis to a similar degree. LiCl significantly altered hedgehog (HH) and Wnt signalling which was associated with inhibited osteogenic gene expression, while fenoldopam demonstrated enhanced early osteogenesis. Long term treatment with both ciliotherapies did not enhance osteogenesis, however LiCl had detrimental effects on cell viability. Intriguingly both ciliotherapies enhanced MSC mechanosensitivity as demonstrated by augmented osteogenic gene expression in response to fluid shear, which over longer durations resulted in enhanced matrix deposition per cell. Conclusions: Therefore, ciliotherapies can be utilised to enhance MSC ciliogenesis resulting in enhanced mechanosensitivity, however, only fenoldopam is a viable ciliotherapeutic option to enhance MSC osteogenesis.