Abstract
Context: Evidence suggests that microRNA (miRNA) regulates gene expression and bone tissue homoeostasis of osteoporosis. MiR-152 has found to be abnormally expressed in osteoporosis, but its role in osteoblast differentiation has not been elucidated.Objective: To understand the potential mechanism of miR-152 in osteoblast differentiation via regulation of RICTOR.Materials and methods: The expression of miR-152 and RICTOR were tested in ovariectomized rat models of osteoporosis. Primary osteoblasts and MC3T -E1 cells were assigned into four groups, namely Control, miR-152 inhibitor, miR-control and miR-152 inhibitor + siRICTOR groups. qRT PCR and Western blots were performed to detect the expression of miR-152 and RICTOR, respectively. MTT assay was used to evaluate cell viability, and ALP activity determination and mineralization analyses were also conducted.Results: In ovariectomy-induced osteoporotic rats, miR-152 (3.06 ± 0.35) in femoral tissues increased significantly, while RICTOR (0.31 ± 0.04) decreased. Compared with the Control group, the miR-152 inhibitor group presented appreciable reduction of miR-152 in primary osteoblasts and MC3T3-E1 cells, as well as remarkable increases in RICTOR, p-Akt(s473)/Akt ratio, and osteogenesis-related genes, with enhanced cell viability, ALP activity and mineralization. In comparison with cells in the miR-152 inhibitor group, those in the miR-152 inhibitor + siRICTOR group had no observable difference in miR-152, but were dramatically up-regulated in RICTOR, as well as the corresponding opposite tendencies of other factors.Conclusion: Inhibiting miR-152 promoted osteoblasts differentiation and alleviated osteoporosis by up-regulating RICTOR. Therefore, miR-152 may be an essential mediator of osteoblast differentiation and a new therapeutic strategy for osteoporosis.
Highlights
Osteoporosis is a relatively prevalent degenerative disease that mainly leads to loss of bone mass and microstructural deterioration of bone tissues and eventually increases the susceptibility of patients to bone fractures (Rachner et al 2011)
By detecting the expression level of miR-152 and RICTOR in femoral tissues, we found rats in OVA group had higher miR-152 and lower RICTOR expressions than those in sham operated group (Sham) group
By retrieving and analysing the data on the target gene prediction website microrna.org, we concluded that the 3’UTR region of RICTOR contains a region complementary with and able to bind to miR-152 (Figure 2(A))
Summary
Osteoporosis is a relatively prevalent degenerative disease that mainly leads to loss of bone mass and microstructural deterioration of bone tissues and eventually increases the susceptibility of patients to bone fractures (Rachner et al 2011). As estimated, it is more prevalent in middle-aged and elderly people, and especially, postmenopausal women had approximately over 60% incidence, posing a big threat to the health of the elderly population (Li et al 2013; Spilmont et al 2014). Exploring new targets for controlling osteogenesis of osteoblasts would provide new strategies and methods for the treatment of osteoporosis
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