Recent studies have shown that statins, the most potent inhibitors of 3-hydroxy-2-methylglutaryl coenzyme A (HMG-CoA) reductase, stimulate bone formation in vitro and in rodents by activating the expression of bone morphogenetic protein-2 (BMP-2), one of the most critical osteoblast differentiation-inducing factors. However, the effect of statins on mesenchymal stem cells (MSCs) is yet to be reported. The purpose of this study is to investigate the influence of fluvastatin, lovastatin, and pravastatin, three commonly prescribed lipid-lowering agents, on the proliferation and differentiation of human MSCs. To our surprise, even though fluvastatin and lovastatin effectively suppressed the growth of human MSCs, a neuroglia rather than osteoblast-like morphology was observed after treatment. Interestingly, such morphological change was inhibited by the co-addition of geranylgeranyl pyrophosphate (GGPP). Immunofluorescence staining with antibodies against neuron-, astrocyte-, as well as oligodendrocyte-specific markers confirmed the neuroglial identity of the differentiated cells. However, BMP-2 is unlikely to play a positive role in neuroglial differentiation of MSCs since its expression was down-regulated in fluvastatin-treated cells. Taken together, our results suggest that fluvastatin and lovastatin induce neuroglial differentiation of human MSCs and that these cholesterol-lowering agents might be used in conjunction with MSC transplantation in the future for treating neurological disorders and injuries.
The discoidin domain receptor-1 (DDR1) is a non-integrin collagen receptor recently implicated in the collective cell migration of other cancer types. Previously, we identified an elevated expression of DDR1 in oral squamous cell carcinoma (OSCC) cells. Through the data mining of a microarray dataset composed of matched tumor-normal tissues from forty OSCC patients, we distilled overexpressed genes statistically associated with angiolymphatic invasion, including DDR1, COL4A5, COL4A6 and PDPN. Dual immunohistochemical staining further confirmed the spatial locations of DDR1 and PDPN in OSCC tissues indicative of collective cancer cell invasion. An elevated DDR1 expression at both the transcription and protein level was observed by treating keratinocytes with collagen of fibrillar or basement membrane types. In addition, inhibition of DDR1 kinase activity in OSCC TW2.6 cells disrupted cell cohesiveness in a 2D culture, reduced spheroid invasion in a collagen gel matrix, and suppressed angiolymphatic invasion in xenograft tissues. Taken together, these results suggest that collagen deposition in the affected tissues followed by DDR1 overexpression could be central to OSCC tumor growth and angiolymphatic invasion. Thus, DDR1 inhibitors are potential therapeutic compounds in restraining oral cancer, which has not been previously explored.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.