The combined treatment of insulin and naringin improves bone properties in rats with type 1 diabetes mellitus.

We have studied the effects of individual and combined treatment of insulin (I) and naringin (NAR) on the bone structure and biomechanical properties of femurs from streptozotocin (STZ)-induced diabetic rats. Male Wistar rats were divided into five groups: (1) controls, (2) STZ-induced diabetic rats, (3) STZ-induced diabetic rats treated with I, (4) STZ-induced diabetic rats treated with NAR, and (5) STZ-induced diabetic rats treated with I + NAR. Bone mineral density (BMD), bone histomorphometry, biomechanical testing, and bone biomarker expressions were accomplished in femur of all animals, as well as serum biochemical analyses. The combined treatment of I + NAR increased the body weight and the femur BMD from STZ-induced diabetic rats. The bone biomechanical properties and the bone morphology of the femurs from STZ-induced diabetic rats were also improved by the combined treatment. The increased number of osteoclasts in STZ-induced diabetic rats was partially prevented by I, NAR, or I + NAR. NAR or I + NAR completely blocked the decrease in the number of osteocalcin (+) cells in the femur from STZ-induced diabetic rats. RUNX family transcription factor 2 immunostaining was much lower in STZ-induced diabetic rats than in control animals; the combination of I + NAR totally blocked this effect. The combined treatment not only ameliorated bone quality and function, but also normalized the variables related to glucose metabolism. Therefore, the combination of I + NAR might be a better therapeutic strategy than the individual I or NAR administration to reduce bone complications in diabetic patients.

Antioxidant Fucoidans Obtained from Tropical Seaweed Protect Pre-Osteoblastic Cells from Hydrogen Peroxide-Induced Damage.

Some antioxidant compounds decrease the amount of intracellular reactive oxygen species (ROS) and consequently reduce the deleterious effects of ROS in osteoblasts. Thus, these compounds fight against osteoporosis. Brown seaweeds are a rich source of antioxidant fucose-containing sulfated polysaccharides (fucans and fucoidans). We obtained six fucoidans (FRFs)-F0.3, F0.5, F0.7, F1.0, F1.5, and F2.1-from Dictyota mertensii by proteolytic digestion followed by sequential acetone precipitation. Except for F0.3, all FRFs showed antioxidant activity in different in vitro tests. In pre- osteoblast-like cells (MC3T3-L1) exposed to H2O2-oxidative stress, caspase-3 and caspase-9 were activated, resulting in apoptosis of the cells. We also observed a decrease in superoxide dismutase (SOD) and alkaline phosphatase (ALP) activity. The antioxidant FRFs protected the cells from the oxidative damage caused by H2O2, decreasing intracellular ROS and caspase activation, and increasing SOD activity. The most effective protection against damage was provided by F0.7, F1.5, and F2.1. At 0.5 mg/mL, these FRFs also suppressed the H2O2-mediated inhibition of ALP activity. The data indicated that FRFs F0.7, F1.5, and F2.1 from D. mertensii were antioxidants that protected bone tissue from oxidative stress and could represent possible adjuvants for the treatment of bone fragility through counteracting oxidative phenomena.

The role of under-investigated connexins in musculoskeletal tissue: a brief review with emphasis on bone tissue / El papel de las escasamente investigadas conexinas en el tejido músculo-esquelético: una breve revisión con énfasis en el tejido óseo

Connexins (Cxs) are a family of transmembrane proteins that form gap junctions and hemi-channels, which mediate cell-cell communication between neighboring cells and the respective extracellular milieu in different tissues. Most tissues and cell types throughout the body express one or more Cx proteins, highlighting its importance in regulating cell growth, differentiation, adhesion, migration, cell death and others. Moreover, Cx can propagate intracellular signals through its C-terminus domain, and thus function beyond a mere channel. Cx43 is the most highly expressed and most well studied Cx in bone and musculoskeletal tissues, although Cx40, Cx45, Cx46 and more recently, the Cx37 have been described in bone tissue, along with Cx26, Cx32 and Cx39 in other musculoskeletal tissues. Here, we discuss the basic structure of gap junctions and the role of the Cxs in musculoskeletal tissue, with special focus on Cx37. (AU)

Las conexinas (Cxs) son una familia de proteínas transmembrana que forman uniones en hendidura y hemicanales encargados de mediar la comunicación entre células vecinas y el respectivo medio extracelular en diferentes tejidos. La mayoría de los tejidos y células expresan una o más proteínas conexina, jugando un papel importante en la regulación de la proliferación celular, diferenciación, adhesión, migración y muerte celular, entre otras funciones. Además de actuar como un canal, las conexinas pueden propagar señales intracelulares a través del dominio C-terminal. La Cx43 es la conexina mas expresada y mejor estudiada en el tejido óseo y el músculo, aunque las Cx40, Cx45, Cx46, y mas recientemente Cx37, son también detectadas en el hueso. A su vez la expresión de la Cx26, Cx32 y Cx39 ha sido observada en otros tejidos músculoesqueléticos. En este manuscrito describimos la estructura básica de las uniones tipo gap y el papel que las Cxs, y en especial la Cx37, tienen en tejidos músculo-esqueléticos. (AU)

Experimental tooth movement and photobiomodulation on bone remodeling in rats.

Photobiomodulation (PBM) is a therapy induced by a specific type of laser that affects biologic systems through non-thermal ways. The study of its basic mechanism has gained interest since little is known about the causes of the different effects of this treatment. In the present study, we investigated the action of the PBM application rate changes in the peri-implant tissues in rats subjected to tooth movement in different periods. Wistar rats (±250 g) received an apparatus in the region of the central incisors superiors tightly (70 g) or not, and they were also subjected to one or three PBM sessions. After 7 or 14 days, the rats were subjected to euthanasia and the jaws were dissected and processed for histology. For analysis, serial sections were made that were stained by Picrosirius Red for analysis of collagen fibers, Masson's trichrome for newly formed bone scan, and Hematoxylin-Eosin for quantification of osteoblasts. PBM applied in one or three sessions increased the population of osteoblasts. Still, the application of three sessions of PBM increased the density of collagen fibers and new bone formation compared to the controls. An increase was observed in the interincisal distance in irradiated groups with three PBM sessions and the application of force for both 7 or 14 days. These findings suggest that PBM can contribute positively to the orthodontic movement. So the laser therapy can be used as an adjunct procedure to be performed concurrently for orthodontic treatment in the dental clinic.

Graphene oxide/multi-walled carbon nanotubes as nanofeatured scaffolds for the assisted deposition of nanohydroxyapatite: characterization and biological evaluation.

Nanohydroxyapatite (nHAp) is an emergent bioceramic that shows similar chemical and crystallographic properties as the mineral phase present in bone. However, nHAp presents low fracture toughness and tensile strength, limiting its application in bone tissue engineering. Conversely, multi-walled carbon nanotubes (MWCNTs) have been widely used for composite applications due to their excellent mechanical and physicochemical properties, although their hydrophobicity usually impairs some applications. To improve MWCNT wettability, oxygen plasma etching has been applied to promote MWCNT exfoliation and oxidation and to produce graphene oxide (GO) at the end of the tips. Here, we prepared a series of nHAp/MWCNT-GO nanocomposites aimed at producing materials that combine similar bone characteristics (nHAp) with high mechanical strength (MWCNT-GO). After MWCNT production and functionalization to produce MWCNT-GO, ultrasonic irradiation was employed to precipitate nHAp onto the MWCNT-GO scaffolds (at 1-3 wt%). We employed various techniques to characterize the nanocomposites, including transmission electron microscopy (TEM), Raman spectroscopy, thermogravimetry, and gas adsorption (the Brunauer-Emmett-Teller method). We used simulated body fluid to evaluate their bioactivity and human osteoblasts (bone-forming cells) to evaluate cytocompatibility. We also investigated their bactericidal effect against Staphylococcus aureus and Escherichia coli. TEM analysis revealed homogeneous distributions of nHAp crystal grains along the MWCNT-GO surfaces. All nanocomposites were proved to be bioactive, since carbonated nHAp was found after 21 days in simulated body fluid. All nanocomposites showed potential for biomedical applications with no cytotoxicity toward osteoblasts and impressively demonstrated a bactericidal effect without the use of antibiotics. All of the aforementioned properties make these materials very attractive for bone tissue engineering applications, either as a matrix or as a reinforcement material for numerous polymeric nanocomposites.