Luminescent carbon quantum dots (CQDs) prepared from aqueous beetroot extract were developed as unique fluorescent nanomaterials for in vivo live animal imaging applications.
We evaluated the bone regeneration and healing effect of Medicarpin (med) in cortical bone defect model that heals by intramembranous ossification. For the study, female Sprague–Dawley rats were ovariectomized and rendered osteopenic. A drill hole injury was generated in mid femoral bones of all the animals. Med treatment was commenced the day after and continued for 15 days. PTH was taken as a reference standard. Fifteen days post-treatment, animals were sacrificed. Bones were collected for histomorphometry studies at the injury site by micro-computed tomography (μCT) and confocal microscopy. RNA and protein was harvested from newly generated bone. For immunohistochemistry, 5μm sections of decalcified femur bone adjoining the drill hole site were cut. By μCT analysis and calcein labeling of newly generated bone it was found that med promotes bone healing and new bone formation at the injury site and was comparable to PTH in many aspects. Med treatment led to increase in the Runx-2 and osteocalcin signals indicating expansion of osteoprogenitors at the injury site as evaluated by qPCR and immunohistochemical localization. It was observed that med promoted bone regeneration by activating canonical Wnt and notch signaling pathway. This was evident by increased transcript and protein levels of Wnt and notch signaling components in the defect region. Finally, we confirmed that med treatment leads to elevated bone healing in pre-osteoblasts by co localization of beta catenin with osteoblast marker alkaline phosphatase. In conclusion, med treatment promotes new bone regeneration and healing at the injury site by activating Wnt/canonical and notch signaling pathways. This study also forms a strong case for evaluation of med in delayed union and non-union fracture cases.
Wnt signaling pathway plays important role in all aspects of skeletal development which include chondrogenesis, osteoblastogenesis, and osteoclastogenesis. Induction of the Wnt-3 signaling pathway promotes bone formation while inactivation of the pathway leads to bone related disorders like osteoporosis. Wnt signaling thus has become a desired target to treat osteogenic disorders. MicroRNAs (miRNAs) represent an important category of elements that interact with Wnt signaling molecules to regulate osteogenesis. Here, we show that miR-376c, a well-characterized tumor suppressor which inhibits cell proliferation and invasion in osteosarcoma by targeting to transforming growth factor-alpha, suppresses osteoblast proliferation, and differentiation. Over-expression of miR-376c inhibited osteoblast differentiation, whereas inhibition of miR-376c function by antimiR-376c promoted expression of osteoblast-specific genes, alkaline phosphatase (ALP) activity, and matrix mineralization. Target prediction analysis tools and experimental validation by luciferase 3' UTR reporter assay along with qRT-PCR identified Wnt-3 and ARF-GEF-1 as direct targets of miR-376c. It was seen that over-expression of miR-376c leads to repression of canonical Wnt/β-catenin signaling. Our overall results suggest that miR-376c targets Wnt-3 and ARF-GEF-1 suppresses ARF-6 activation which prevents the release of β-catenin and its transactivation thereby inhibiting osteoblast differentiation. Although miR-376c is known to be a tumor repressor; we have identified a second complementary function of miR-376c where it inhibits Wnt-3-mediated osteogenesis and promotes bone loss.
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