Bone repair involves bone resorption through osteoclastogenesis and the stimulation of neovascularization and osteogenesis by endothelial progenitor cells (
EPC
s). However, the role of
EPC
s in osteoclastogenesis is unclear. In this study, we assess the effects of
EPC
‐derived exosomes on the migration and osteoclastic differentiation of primary mouse bone marrow‐derived macrophages (
BMM
s) in vitro using immunofluorescence, western blotting,
RT
‐
PCR
and Transwell assays. We also evaluated the effects of
EPC
‐derived exosomes on the homing and osteoclastic differentiation of transplanted
BMM
s in a mouse bone fracture model in vivo. We found that
EPC
s cultured with
BMM
s secreted exosomes into the medium and, compared with
EPC
s, exosomes had a higher expression level of Lnc
RNA
‐
MALAT
1. We confirmed that Lnc
RNA
‐
MALAT
1 directly binds to miR‐124 to negatively control miR‐124 activity. Moreover, overexpression of miR‐124 could reverse the migration and osteoclastic differentiation of
BMM
s induced by
EPC
‐derived exosomes. A dual‐luciferase reporter assay indicated that the integrin
ITGB
1 is the target of miR‐124. Mice treated with
EPC
‐derived exosome‐
BMM
co‐transplantations exhibited increased neovascularization at the fracture site and enhanced fracture healing compared with those treated with
BMM
s alone. Overall, our results suggest that
EPC
‐derived exosomes can promote bone repair by enhancing recruitment and differentiation of osteoclast precursors through Lnc
RNA
‐
MALAT
1.
The antitumor effects of curcumin have attracted widespread attention worldwide. One of its major functions is to induce the apoptosis of tumor cells, but the antitumor mechanism is currently unclear. In the present study, we found that cell mortality and curcumin concentration were dose dependent. Curcumin of low concentrations (10 μΜ) could reduce the level of reactive oxygen species (ROS) in tumor cells, while curcumin of high concentrations (80 μΜ) was able to significantly increase the content of ROS. In addition, Western blotting detection suggested that curcumin of high concentrations can induce the release of Cyto-C and the activation of Caspase-3, and that ROS scavenger NAC apparently inhibits apoptosis protein release and activation, consequently slowing the curcumin-induced apoptosis. Taken together, curcumin further activates the mitochondrial apoptotic pathway by inducing cells to generate ROS and ultimately promotes the apoptosis of tumor cells.
Dihydroartemisinin (DHA) is a widely used antimalarial drug isolated from the plant Artemisia annua. Recent studies suggested that DHA has antitumor effects utilizing its reactive oxygen species (ROS) yielding mechanism. Here, we reported that DHA is inhibitory on lipopolysaccharide (LPS)-induced osteoclast (OC) differentiation, fusion and bone-resorption activity in vitro. Intracellular ROS detection revealed that DHA could remarkably increase ROS accumulation during LPS-induced osteoclastogenesis. Moreover, cell apoptosis was also increased by DHA treatment. We found that DHA-activated caspase-3 increased Bax/Bcl-2 ratio during LPS-induced osteoclastogenesis. Meanwhile, the translocation of apoptotic inducing factor (AIF) and the release of cytochrome c from the mitochondria into the cytosol were observed, indicating that ROS-mediated mitochondrial dysfunction is crucial in DHA-induced apoptosis during LPS-induced osteoclastogenesis. In vivo study showed that DHA treatment decreased OC number, prevents bone loss, rescues bone microarchitecture and restores bone strength in LPS-induced bone-loss mouse model. Together, our findings indicate that DHA is protective against LPS-induced bone loss through apoptosis induction of osteoclasts via ROS accumulation and the mitochondria-dependent apoptosis pathway. Therefore, DHA may be considered as a new therapeutic candidate for treating inflammatory bone loss.
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