Abstract
This study aimed to investigate the effects of fluvastatin on the differentiation of bone marrow stromal cells (BMSCs) into osteoblasts in senescence-accelerated mouse prone 6 (SAMP6) compared with that in the normal senescence-accelerated-resistant mouse (SAMR1) model. SAMP strains arose spontaneously from the AKR/J background and display shortened life span and an array of signs of accelerated aging, compared with control SAMR strains. The dose effects of fluvastatin were also evaluated. BMSCs were cultured with/without fluvastatin (0 μM, 0.1 μM, 0.5 μM, and 1.0 μM). WST-1-based colorimetry was performed to evaluate cell proliferation. To evaluate cell differentiation, gene expression levels of bmp2 and runx2 were determined by quantitative reverse transcription polymerase chain reaction (qRT-PCR), and protein expression levels were determined using enzyme-linked immunosorbent assay (BMP2) and immunofluorescence staining (BMP2 and Runx2). Alkaline phosphatase (ALP) activity assay and histochemical detection were determined; the effect of noggin, a BMP-specific antagonist, was examined using ALP histochemical detection. To assess for mature osteogenic marker, gene expression levels of bglap2 were determined by qRT-PCR and mineralization was determined by alizarin red staining. RhoA activity was also examined by Western blotting. In SAMP6, BMP2, Runx2 and Bglap2 mRNA and protein expressions were significantly increased by fluvastatin, and ALP activity was increased by BMP2 action. RhoA activity was also inhibited by fluvastatin. The concentration of fluvastatin sufficient to increase BMP2 and Runx2 expression and ALP activity was 0.5 μM in SAMP6 and 0.1 μM in SAMR1. In conclusion, the present study revealed that fluvastatin promoted BMSC differentiation into osteoblasts by RhoA-BMP2 pathway in SAMP6. BMSCs of SAMP6 are less sensitive to the osteogenic effects of fluvastatin than SAMR1.
Highlights
No significant differences in cell proliferation were associated with differences in concentrations of fluvastatin in SAMR1 and senescence-accelerated mouse prone 6 (SAMP6) on any day (Fig 1A and 1B)
In SAMR1 bone marrow stromal cells (BMSCs), bmp2 mRNA expression was significantly increased at fluvastatin concentrations more than 0.1 μM at 3 days and 7 days of culture (Fig 1C), whereas bmp2 mRNA expression in SAMP6 BMSCs was significantly increased at concentrations >0.5 μM at 3 days and 7 days of culture (Fig 1D)
enzyme linked immunosorbent assay (ELISA) analysis showed that BMP2 concentrations in SAMR1 BMSCs were significantly increased at concentrations >0.1 μM at 3 days of culture (Fig 1E)
Summary
The number of elderly patients who receive implant treatment is increasing [1]. Osteoporosis, including high-turnover and lowturnover osteoporosis, is a well-known risk factor for the prognosis of dental implants [2]. In high-turnover osteoporosis, bone resorption increases because of estrogen deficiency; in low-turnover osteoporosis, the ossification potential is compromised because of aging [3]. Low-turnover osteoporosis is observed in women and in men [3]. Several studies regarding high-turnover osteoporosis have been performed, whereas studies regarding lowturnover osteoporosis are scarce. Investigation of low-turnover osteoporosis is important for treatment of elderly people
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