Abstract
This study aimed to preliminary investigate the role of activin receptor-like kinase (ALK) 5 as one of TGF-βR1 subtypes in bone turnover and osteoblastic differentiation induced by fluoride. We analyzed bone mineral density and the expression of genes related with transforming growth factor-β1(TGF-β1) signaling and bone turnover in rats treated by different concentrations of fluoride with or without SB431542 in vivo. Moreover, MTT assay, alkaline phosphatase staining, RT-PCR, immunocytochemical analysis and western blot analysis were used to detect the influence on bone marrow stem cells (BMSC) after stimulating by varying concentration of fluoride with or without SB431542 in vitro. The in vivo study showed SB431542 treatment affected bone density and gene expression of rats, which indicated TGF-β1 and ALK5 might take part in fluoride-induced bone turnover and bone formation. The in vitro study showed low concentration of fluoride improved BMSC cells viability, alkaline phosphatase activity, and osteocalcin protein expression which were inhibited by high concentration of fluoride. The gene expression of Runx2 and ALK5 in cells increased after low concentration fluoride treatment which was also inhibited by high concentration of fluoride. Fluoride treatment inhibited gene and protein expression of Samd3 (except 1 mgF-/L). Compared with fluoride treatment alone, cells differentiation was inhibited with SB431542 treatment. Moreover, the expression of Runx2, ALK5 and Smad3 were influenced by SB431542 treatment. In conclusion, this preliminary study indicated that fluoride regulated osteoblastic TGFβ1 signaling in bone turnover and cells differentiation via ALK5.
Highlights
Fluoride is an important element for human in maintaining bone strength and stimulates bone growth [1]
Gene expression ofRunx2, RANKL, ALK5 and Smad3 was detected in bone tissue
Results showed that gene expression ofRunx2 slightly enhanced after low-dose fluoride treatment, but decreased in high-dose fluoride group compared with control group
Summary
Fluoride is an important element for human in maintaining bone strength and stimulates bone growth [1]. It regulates bone formation by enhancing osteoblast differentiation and stimulating alkaline phosphatase (ALP) activity, which considered a marker for osteoblast [2,3]. Excessive fluoride may result in skeletal fluorosis, a condition that patients display various bone lesions including osteosclerosis, osteoporosis and degenerative joint changes [4,5]. Some investigators have reported many studies in fluoride and bone turnover [6,7], the pathogenic mechanism of the skeletal fluorosis was still unclear.
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