Anabolic Bone Formation Via a Site-Specific Bone-Targeting Delivery System by Interfering With Semaphorin 4d Expression

Abstract

Semaphorins have been recently targeted as new molecules directly implicated in the cell-cell communication that occurs between osteoclasts and osteoblasts. Overexpression of certain semaphorins, such as semaphorin4D (sema4D), is found in an osteoporotic phenotype and plays a key role in osteoclast activity by suppressing osteoblast maturation, thus significantly altering the bone modeling cycle. In the present study, we fabricate a site-specific bone-targeting drug-delivery system from polymeric nanoparticles with the incorporation of siRNA interference molecule for sema4D and demonstrate their cellular uptake and intracellular trafficking within osteoclasts, thus preventing the suppression of osteoblast activity. We then demonstrate in an osteoporotic animal model induced by ovariectomy that weekly intravenous injections led to a significantly greater number of active osteoblasts at the bone surface, resulting in higher bone volume in compromised animals. The findings from the present study demonstrate a novel and promising site-specific therapeutic option for the treatment of osteoporosis via interference of the sema4D-plexin cell communication pathway between osteoclasts and osteoblasts.

Behavior of Gingival Fibroblasts on Titanium Implant Surfaces in Combination with either Injectable-PRF or PRP

“…After seven days of culture, total RNA was isolated from cells using AxyPrep™ Multisource Total RNA Miniprep Kit (AXYGEN, Union City, CA, USA) according to the manufacturer’s protocol. The RNA concentration was determined by a NanoDrop 2000 UV-Vis Spectrophotometer as previously described [50]. A total of 1 µg RNA solution was immediately reverse transcribed to cDNA using a First Strand cDNA Synthesis Kit (GeneCopoeia, Rockville, MD, USA) and the final volume is 100 µL.…”

Initial changes in alveolar bone volume for sham-operated and ovariectomized rats in ligature-induced experimental periodontitis

“…Analysis of the furcation area was assessed for the presence of osteoclasts as defined by cells with greater than three nuclei and counted at the various time points as previously described [22]. Samples were assessed for their staining intensity with respect to alveolar bone loss adjacent to the periodontal ligament in the furcation area along the PDL-bone perimeter.…”

Bone grafting material in combination with Osteogain for bone repair: a rat histomorphometric study

“…Areas of newly formed bone, which acquired a red color in H&E-stained sections and a bluish-green stain in Safranin O-stained sections, were delineated manually and then calculated as the percentage of new bone area in total cross-sectional area [(bone area/ total area)×100 %] as previously described [19,[23][24][25]. The central region of the 2.5-mm-diameter defect was defined by analyzing a circular contour as area of measurement per slice, thus to obtain a consistent volume of interest and to avoid including the native bone margins.…”