No abstract

MicroRNAs (miRNAs) have been widely demonstrated to interact with multiple cellular signaling pathways and to participate in a wide range of physiological processes. Estradiol-17β (E2) is the most potent and prevalent endogenous estrogen that plays a vital role in promoting bone formation and reducing bone resorption. Currently, little is known about the regulation of miRNAs in E2-induced osteogenic differentiation. In the present study, the primary bone marrow mesenchymal stem cells from rats (rBMSCs) were isolated and incubated with E2, followed by miRNA profiling. The microarray showed that 29 miRNAs were differentially expressed in response to E2 stimulation. Further verification by real-time reverse-transcriptase polymerase chain reaction revealed that E2 enhanced the expression of let-7b and miR-25 but suppressed the miR-30b expression. Moreover, a gain-of-function experiment confirmed that miR-30b negatively regulated the E2-induced osteogenic differentiation. These data suggest an important role of miRNAs in osteogenic differentiation.

Bone regeneration strategies rely on biomaterial constructs with stem cells or growth factors. By comparison, cell homing strategies employ chemokines to recruit the host endogenous stem or progenitor cells to the defect site to support endogenous healing. In the present study, we used a novel fluffy hydroxyapatite/polyacrylonitrile (HA/PAN) composite scaffold to provide a better three-dimensional cell culture microenvironment. These HA/PAN composite scaffolds loaded with stromal cell-derived factor-1α (SDF-1α) provided a diffusion-controlled SDF-1α release profile and endowed the scaffolds with cell homing capabilities. Furthermore, the scaffolds significantly stimulated bone marrow stromal cell (BMSC) recruitment, facilitated BMSC osteogenic differentiation, and promoted ectopic bone formation. Our results suggest that a HA/PAN composite scaffold loaded with SDF-1α offers a clinically beneficial bone repair strategy.