Role In Bone Disorders Research Articles

Chitosan/montmorillonite composite nanospheres for sustained antibiotic delivery at post-implantation bone infection treatment

Despite the advancements in bone transplantation operations, inflammation is still a serious problem that threatens human health at the post-implantation period. Conventional antibiotic therapy methods may lead to some side effects such as ototoxicity and nephrotoxicity, especially when applied in high doses. Therefore, local drug delivery systems play a vital role in bone disorders due to the elimination of the disadvantages introduced by conventional methods. In the presented study, it was aimed to develop Vancomycin (VC) and Gentamicin (GC) loaded chitosan-montmorillonite nanoclay composites (CS/MMT) to provide required antibiotic doses to combat post-implantation infection. CS/MMT nanocomposite formation was supplied by microfluidizer homogenization and spherical drug carrier nanoparticles were obtained by electrospraying technique. Three factors; voltage, distance and flowrate were varied to fabricate spherical nanoparticles with uniform size. Emprical model was developed to predict nanosphere size by altering process variables. Nanospheres were characterized in terms of morphology, hydrodynamic size, zeta potential, drug encapsulation efficiency and release profile. Drug loaded nanospheres have been successfully produced with a size range of 180–350 nm. Nanocomposite drug carriers showed high encapsulation efficiency (80%–95%) and prolonged release period when compared to bare chitosan nanospheres. The drug release from nanocomposite carriers was monitored by diffusion mechanism up to 30 d. The in vitro release medium of nanospheres showed strong antimicrobial activity against gram-positive S. aureus and gram-negative E. coli bacteria. Furthermore, it was found that the nanospheres did not show any cytotoxic effect to fibroblast (NIH/3T3) and osteoblast (SaOS-2) cell lines. The results demonstrated that the prepared composite nanospheres can be a promising option for bone infection prevention at the post implantation period.

Paeoniflorin Inhibits Receptor Activator for Nuclear Factor κB (RANK) Ligand-Induced Osteoclast Differentiation In Vitro and Particle-Induced Osteolysis In Vivo.

BackgroundPaeoniflorin (PF), a glucoside isolated from the dried root of Paeonia lactiflora Pall, has been reported to have a number of pharmacological properties, including immunity-regulation, anticancer activities, and neuroprotective effect. However, PF’s pharmacological role in bone disorder has been seldom reported. Hence, this study was designed to investigate the effects of PF on osteoclast differentiation and osteolysis diseases.Material/MethodsThe bone marrow macrophages were isolated from C57BL/6 mice and incubated with RANK ligand (RANKL) and various concentrations of PF. After 5 days of incubation, tartrate-resistant acid phosphatase (+) cells and bone resorption pits were counted. Effects of PF on expression of osteoclast-specific protein and gene were investigated via Western blot, q-PCR, and immunofluorescence assay. The osteoprotective effect of PF in vivo was evaluated in a calvarial osteolysis model via micro-CT scan and histological stain.ResultsIn vitro, PF intervention inhibited osteoclast formation and resorption activity. PF also impaired RANKL-induced NF-κB phosphorylation and immigration to the nucleus. PF suppressed osteoclast-marker protein and gene expression. In vivo, PF inhibited cobalt-chromium-molybdenum alloy particle-induced osteolysis and reduced osteoclast number in tissue slice.ConclusionsPF is a potential agent against osteolysis-related diseases caused by excessive osteoclast activity.

Alpinumisoflavone inhibits osteoclast differentiation and exerts anti-osteoporotic effect in ovariectomized mice

Alpinumisoflavone (AIF), a naturally occurring flavonoid compound exacted from Derris eriocarpa, has been found to have a number of pharmacological activities. However, its role in bone disorder has not been investigated. The aim of this study is to evaluate the osteoprotective effect of AIF on ovariectomy-induced bone loss in mice model and related underlying mechanisms. Our study provides experimental evidence that AIF could regulate the remodeling process of bone and exert osteoprotective effect against ovariectomy-induced bone loss. Moreover, our results show that AIF suppresses osteoclast differentiation by attenuating RANKL-induced activation of p38, ERK and JNK pathways and consequently represses the expression of c-Fos and NFATc1.

Role of nutritional zinc in the prevention of osteoporosis

Zinc is known as an essential nutritional factor in the growth of the human and animals. Bone growth retardation is a common finding in various conditions associated with dietary zinc deficiency. Bone zinc content has been shown to decrease in aging, skeletal unloading, and postmenopausal conditions, suggesting its role in bone disorder. Zinc has been demonstrated to have a stimulatory effect on osteoblastic bone formation and mineralization; the metal directly activates aminoacyl-tRNA synthetase, a rate-limiting enzyme at translational process of protein synthesis, in the cells, and it stimulates cellular protein synthesis. Zinc has been shown to stimulate gene expression of the transcription factors runt-related transcription factor 2 (Runx2) that is related to differentiation into osteoblastic cells. Moreover, zinc has been shown to inhibit osteoclastic bone resorption due to inhibiting osteoclast-like cell formation from bone marrow cells and stimulating apoptotic cell death of mature osteoclasts. Zinc has a suppressive effect on the receptor activator of nuclear factor (NF)-kappaB ligand (RANKL)-induced osteoclastogenesis. Zinc transporter has been shown to express in osteoblastic and osteoclastic cells. Zinc protein is involved in transcription. The intake of dietary zinc causes an increase in bone mass. beta-Alanyl-L: -histidinato zinc (AHZ) is a zinc compound, in which zinc is chelated to beta-alanyl-L: -histidine. The stimulatory effect of AHZ on bone formation is more intensive than that of zinc sulfate. Zinc acexamate has also been shown to have a potent-anabolic effect on bone. The oral administration of AHZ or zinc acexamate has the restorative effect on bone loss under various pathophysiologic conditions including aging, skeletal unloading, aluminum bone toxicity, calcium- and vitamin D-deficiency, adjuvant arthritis, estrogen deficiency, diabetes, and fracture healing. Zinc compounds may be designed as new supplementation factor in the prevention and therapy of osteoporosis.