Insulin growth factor binding protein-3 enhances dental implant osseointegration against methylglyoxal-induced bone deterioration in a rat model.

PURPOSE: The aim of this study was to determine the effect of insulin growth factor binding protein-3 (IGFBP-3) on the inhibition of glucose oxidative stress and promotion of bone formation near the implant site in a rat model of methylglyoxal (MGO)-induced bone loss. METHODS: An in vitro study was performed in MC3T3 E1 cells treated with chitosan gold nanoparticles (Ch-GNPs) conjugated with IGFBP-3 cDNA followed by MGO. An in vivo study was conducted in a rat model induced by MGO administration after the insertion of a dental implant coated with IGFBP-3. RESULTS: MGO treatment downregulated molecules involved in osteogenic differentiation and bone formation in MC3T3 E1 cells and influenced the bone mineral density and bone volume of the femur and alveolar bone. In contrast, IGFBP-3 inhibited oxidative stress and inflammation and enhanced osteogenesis in MGO-treated MC3T3 E1 cells. In addition, IGFBP-3 promoted bone formation by reducing inflammatory proteins in MGO-administered rats. The application of Ch-GNPs conjugated with IGFBP-3 as a coating of titanium implants enhanced osteogenesis and the osseointegration of dental implants. CONCLUSIONS: This study demonstrated that IGFBP-3 could be applied as a therapeutic component in dental implants to promote the osseointegration of dental implants in patients with diabetes, which affects MGO levels.

Mussel adhesive protein blended with gelatin loaded into nanotube titanium dental implants enhances osseointegration.

The purpose of this study was to investigate whether mussel adhesive protein (MAP) blended with gelatin loaded into nanotube titanium (Ti) dental implants enhances osseointegration and supports bone formation. Cell viability, crystal violet staining, Western blot analysis, alizarin red S staining, alkaline phosphatase (ALP) activity, micro-computed tomography (µ-CT), hematoxylin and eosin (H&E), and immunohistochemistry (IHC) staining were employed to test the biocompatibility of MAP blended with gelatin (MAP/Gel). MC3T3 E1 cells were used for in vitro and Sprague-Dawley rats for in vivo models in this study. MC3T3 E1 cells cultured in MAP/Gel loaded into nanotube Ti surface demonstrated activation of FAK-PI3K-MAPKs-Wnt/ß-catenin signaling pathway and enhanced osteogenic differentiation. µ-CT, H&E, and IHC staining confirmed that MAP/Gel dental implants promoted bone regeneration around the nanotube Ti implants by upregulation of Runx-2, BMP-2/7, Osterix, and OPG in rat mandible model. MAP/Gel supports osseointegration of dental implant after implantation. It is hypothesized that MAP/Gel loaded into nanotube Ti dental implants may be applicable as a potential treatment for bone formation and proper integration of dental implants with alveolar bone. Graphical abstract.

Guided bone regeneration with a gelatin layer and adenoviral delivery of c-myb enhances bone healing in rat tibia.

Aim: Bone healing becomes problematic during certain states, such as trauma. This study verifies whether the application of c-myb with gelatin promotes bone healing during bone injuries. Materials & methods: A biodegradable membrane was modified with adenoviral vector c-myb (Ad/c-myb) and gelatin and applied in the bone injury site of rat tibia. Results:c-myb enhanced osteogenic differentiation and mineralization in bone marrow stromal cells after induction with osteogenic media. In vivo examination of rat tibia after application of the biodegradable membrane with Ad/c-myb and a gelatin layer demonstrated increased bone volume, bone mineral density, new bone formation and osteogenic molecules, compared with Ad/LacZ. Conclusion:c-myb has the potential to assist bone healing and may be applicable to the treatment of bone during injury.

Effect of gomisin A on osteoblast differentiation in high glucose-mediated oxidative stress.

BACKGROUND: Gomisin A is a lignan isolated from the hexane of Schisandra chinensis fruit extract with antioxidant properties. Oxidative stress mediated by high glucose is one of the major complications of diabetes mellitus. PURPOSE: This study investigates the role of gomisin A in osteoblast differentiation under high glucose-induced oxidative stress in MC3T3 E1 cells and determines its relationship with heme oxygenase-1 (HO-1) and mitochondrial biogenesis. METHODS: MC3T3 E1 cells were treated by gomisin A following induced by high glucose levels and glucose oxidase to investigate the inhibitory effect of gomisin A against high glucose oxidative stress. Western blot analysis, alizarin red staining, alkaline phosphatase (ALP) activity, analysis of reactive oxygen species (ROS) and confocal microscopy were used to determine mitochondrial biogenesis, oxidative stress, osteoblast differentiation and mineralization. To analyze the role of HO-1, the MC3T3 E1 cells were treated with the HO-1 inhibitor zinc protoporphyrin IX (ZnPP). RESULTS: Gomisin A enhanced the expression of HO-1, increased mitochondrial biogenesis factors (peroxisome proliferator-activated receptor gamma coactivator 1-alpha, nuclear respiratory factor-1, and mitochondrial transcription factor A), antioxidant enzymes (copper-zinc superoxide dismutases and manganese superoxide dismutase), osteoblast differentiation molecules (bone morphogenic protein-2/7, osteoprotegerin and Runt-related transcription factor-2) and mineralization by upregulation of ALP and alizarin red staining, which were decreased by ZnPP and high glucose oxidative stress. Similarly, gomisin A inhibited ROS which was increased by ZnPP and the high glucose-mediated oxidative stress. CONCLUSIONS: The findings demonstrated the antioxidative effects of gomisin A, and its role in mitochondrial biogenesis and osteoblast differentiation. It potentially regulated osteoblast differentiation under high glucose-induced oxidative stress via upregulation of HO-1 and maintenance of mitochondrial homeostasis. Thus, gomisin A may represent a potential therapeutic agent for prevention of bone fragility fractures and implant failure triggered by diabetes.

Schisandra chinensis extract ameliorates age-related muscle wasting and bone loss in ovariectomized rats.

Exercise and healthy diet consumption support healthy aging. Schisandra chinensis (Turcz.) also known as "Baill." has anti-inflammatory and antioxidant properties. However, the role of S. chinensis as an antiaging compound has yet to be demonstrated. This study elucidated the antiaging effect of S. chinensis ethanol-hexane extract (C1) and the effect of C1 treatment on muscle and bone following physical exercise in ovariectomized (OVX) rats. RAW 264.7, human diploid fibroblasts (HDFs), C2C12 myoblasts, bone marrow macrophages, and MC3T3-E1 cells were used for in vitro, and muscle and bone of OVX rats were used for in vivo study to demonstrate the effect of C1. The C1 significantly inhibited the expression of inflammatory molecules, ß-galactosidase activity, and improved antioxidant activity via down-regulation of reactive oxygen species in RAW 264.7 and aged HDF cells. The C1 with exercise improved muscle regeneration in skeletal muscle of OVX rats by promoting mitochondrial biogenesis and autophagy. C1 induced osteoblast differentiation, and C1 + exercise modulated the bone formation and bone resorption in OVX rats. C1 exhibited anti-inflammatory, antioxidant, myogenic, and osteogenic effects. C1 with exercise improved age-related muscle wasting and bone loss. Therefore, S. chinensis may be a potential prevent agent for age-related diseases such as sarcopenia and osteoporosis.

Chitosan-gold nanoparticles mediated gene delivery of c-myb facilitates osseointegration of dental implants in ovariectomized rat.

Osseointegration of dental implants is affected by osteoporosis. The purpose of this study was overcome the implant failure and facilitate the osseointegration of dental implants by c-myb in ovariectomized (OVX)-induced osteoporosis. c-myb is a transcription factor and supports bone formation. Plasmid DNA/c-myb conjugated with chitosan-gold nanoparticles (Ch-GNPs/c-myb) promoted osteogenesis and inhibited osteoclastogenesis in MC-3T3 E1 cells. Ch-GNPs/c-myb involved the reduction of the nuclear factor of activated T-cells 1, c-Fos, and tartrate-resistant acid phosphatase-positive multinucleated osteoclasts in receptor activator of nuclear factor-κB ligand (RANKL) stimulated bone marrow macrophages. In vivo results of rat mandibles demonstrated Ch-GNP/c-myb-coated titanium (Ti) implants increased the volume and density of newly formed bone and the osseointegration of dental implant with bone by micro computed tomography examination after OVX-induced osteoporosis. Immunohistochemical analysis showed increased c-myb expression and upregulation of bone morphogenic proteins, osteoprotegerin and EphB4, as well as the downregulation of RANKL by Ch-GNP/c-myb-coated Ti implants. Hematoxylin and Eosin staining expressed new bone formation by Ch-GNP/c-myb-coated Ti implants. Our findings indicated that c-myb delivered by Ch-GNPs supports osseointegration of dental implant even in osteoporotic condition. c-myb may be applicable to support dental implant integration and treatment in age-dependent bone destruction disease.

Phelligridin D-loaded oral nanotube titanium implant enhances osseointegration and prevents osteolysis in rat mandible.

Poor bone quality and osteolysis are the major causes of implant failure in dentistry. Here, this study tested the effect of phelligridin D-loaded nanotubes titanium (Ti) for bone formation around the dental implants. The purpose of this study was to enhance osseointegration of phelligridin D-loaded implant into the bone for bone formation and prevention of osteolysis. Cell viability, crystal violet staining, Western blot, alizarin red S staining, alkaline phosphatase activity, tartrate-resistant acid phosphatase staining, micro-computed tromography (µ-CT), hematoxylin and eosin (H&E) and immunohistochemical staining were used in vitro and in vivo to test the biocompatibility of phelligridin D. Phelligridin D enhanced osteoblast differentiation and mineralization by increasing bone morphogenic protein-2/7 (BMP-2/7), Osterix, Runx-2, osteoprotegerin (OPG), alkaline phosphatase and inhibited osteoclast differentiation by decreasing receptor activator of nuclear factor kappa-B ligand (RANKL) in MC-3T3 E1 cells. Further, phelligridin D promoted bone regeneration around nanotube Ti implant surface by increasing the levels of BMP-2/7 and OPG in a rat model. Phelligridin D also inhibited osteolysis by suppressing the expression of RANKL. These findings strongly suggest that phelligridin D is a new compound representing a potential therapeutic candidate for implant failure caused by osteolysis and poor bone quality of teeth.

Schisandrin C enhances odontoblastic differentiation through autophagy and mitochondrial biogenesis in human dental pulp cells.

OBJECTIVE: To investigate the role of Schisandrin C in odontoblastic differentiation, and its relations between autophagy and mitochondrial biogenesis in human dental pulp cells (HPDCs). DESIGN: Fresh third molars were used, and cultured for HDPCs. Western blotting technique, Alizarin red S staining, alkaline phosphatase (ALP) activity, and confocal microscopy were used to detect autophagy, mitochondrial biogenesis, and odontoblastic differentiation. To understand the mechanism of Schisandrin C, the HDPCs were treated with lipopolysaccharide (LPS), autophagy and heme oxygenase-1 (HO-1) inhibitors: 3-Methyladenine (3-MA) and Zinc protoporphyrin IX (ZnPP), respectively. RESULTS: LPS decreased the expression of autophagy molecules [autophagy protein 5 (ATG-5), beclin-1, and microtubule-associated protein 1A/1B light chain 3 (LC3-I/II)] and mitochondrial biogenesis molecules [heme oxygenase-1 (HO-1) and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α)], and disrupted odontoblastic differentiation. The down-regulation of autophagy and mitochondrial biogenesis with 3-MA and ZnPP inhibited odontoblastic differentiation. However, Schisandrin C restored the expression of all the above molecules, even with LPS and inhibitor treatment. This result demonstrates that autophagy and mitochondrial biogenesis plays an essential role in odontoblastic differentiation, and Schisandrin C activates these systems to promote odontoblastic differentiation of HDPCs. CONCLUSION: Schisandrin C has potential characters to regulate odontoblastic differentiation, and may be recommended for use as a compound for pulp homeostasis.

Pattern of thyroid dysfunction in patients with metabolic syndrome and its relationship with components of metabolic syndrome.

BACKGROUND: Thyroid dysfunction (TD) and metabolic syndrome (MetS) are known risk factors for atherosclerotic cardiovascular disease (ASCVD). TD is risk factor for ASCVD mediated by the effects of thyroid hormones on lipid metabolism and blood pressure hence the components of MetS. It is possible that coexistence of these two disease entities and unrecognized TD in patients with MetS might substantially increase ASCVD risk. Moreover, little is known about the relationship between TD and the components of MetS. Thus, the purpose of this study was to evaluate the pattern of TD in patients with MetS and its relationship with components of the MetS. METHODS: A total of 358 previously diagnosed patients with MetS were recruited in the study. The thyroid function test parameters were measured to classify TD at Dhulikhel Hospital-Kathmandu University Hospital, Dhulikhel, Nepal. Statistical analyses were performed using SPSS version 16.0 to evaluate pattern and relationship. RESULTS: The overall prevalence of TD in patients with MetS was 31.84% with high prevalence of subclinical hypothyroidism (29.32%). We found no evidence of a relationship between TD and components of MetS, although there was significant difference in waist circumference between four groups of TD. CONCLUSION: Patients with MetS had subclinical hypothyroidism greatly. Although there was no evidence of any relationship between thyroid status and all components of MetS, TD should be taken into account when evaluating and treating patients with MetS to reduce the impending risk.