Abstract
Bone fracture is a common medical condition, which may occur due to traumatic injury or disease-related conditions. Evidence suggests that microRNAs (miRNAs) can regulate osteoblast differentiation and function. In this study, we explored the effects and mechanism of miR-221 on the growth and migration of osteoblasts using MC3T3-E1 cells. The expression levels of miR-221 in the different groups were measured by qRT-PCR. Then, miR-221 mimic and inhibitor were transfected into MC3T3-E1 cells, and cell viability and migration were measured using the CCK-8 assay and the Transwell migration assay. Additionally, the expression levels of differentiation-related factors (Runx2 and Ocn) and ZFPM2 were measured by qRT-PCR. Western blot was used to measure the expression of cell cycle-related proteins, epithelial-mesenchymal transition (EMT)-related proteins, ZFPM2, and Wnt/Notch, and Smad signaling pathway proteins. miR-221 was significantly up-regulated in the patients with lumbar compression fracture (LCM) and trochanteric fracture (TF). miR-221 promoted ALP, Runx2, and OPN expressions in MC3T3-E1 cells. miR-221 overexpression significantly increased cell proliferation, migration, differentiation, and matrix mineralization, whereas suppression of miR-221 reversed these effects. Additionally, the results displayed that ZFPM2 was a direct target gene of miR-221, and overexpression of ZFPM2 reversed the promoting effects of miR-221 overexpression on osteoblasts. Mechanistic study revealed that overexpression of miR-221 inactivated the Wnt/Notch and Smad signaling pathways by regulating ZFPM2 expression. We drew the conclusions that miR-221 overexpression promoted osteoblast proliferation, migration, and differentiation by regulation of ZFPM2 expression and deactivating the Wnt/Notch and Smad signaling pathways.
Highlights
Bone fracture is a common and increasing disease, which results from both traumatic injury and disease-related bone fragility [1]
Results miR-221 was up-regulated during osteoblast differentiation
The results showed that the blood concentrations of miR-221 were obviously increased at 7 and 14 days after surgery, whereas the concentrations of miR-221 was recovered at 21 days after surgery (Figure 1A and B)
Summary
Bone fracture is a common and increasing disease, which results from both traumatic injury and disease-related bone fragility [1]. Bone fracture may lead to fever, disability, shock, and treatment is very expensive. And appropriate management of bone fractures can help patients restore original functions. Bone fracture healing is a physiologically complex process, which involves both biological and mechanical factors [4]. A series of events occurs, including cell migration, differentiation, tissue synthesis, and the release of cytokines and growth factors. The recovery process of fracture depends on the activity of osteoblasts [5,6]. Osteoblasts are mesenchymal cells, which play a major role in skeletal development and bone formation [7]. Osteoblasts are responsible for the synthesis, secretion and mineralization of bone matrix [8]. It is necessary to explore the mechanism of osteoblast proliferation, migration, and differentiation
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