Increased osteoclastogenesis is responsible for osteolysis, which is a severe consequence of inflammatory diseases associated with bone destruction, such as rheumatoid arthritis and periodontitis. The mechanisms that limit osteoclastogenesis under inflammatory conditions are largely unknown. We previously identified transcription factor RBP-J as a key negative regulator that restrains TNF-α–induced osteoclastogenesis and inflammatory bone resorption. In this study, we tested whether RBP-J suppresses inflammatory osteoclastogenesis by regulating the expression of microRNAs (miRNAs) important for this process. Using high-throughput sequencing of miRNAs, we obtained the first, to our knowledge, genome-wide profile of miRNA expression induced by TNF-α in mouse bone marrow–derived macrophages/osteoclast precursors during inflammatory osteoclastogenesis.
Outstanding Mechanical Response and Bone Regeneration Capacity of Robocast Dilute Magnesium-doped Wollastonite Scaffolds in Critical Size Bone Defect
The regeneration and repair of damaged load-bearing segmental bone requires considerable mechanical strength for the artificial implants. The ideal biomaterials should also facilitate the production of porous implants with high bioactivity desirable for stimulating new bone growth. Here we developed a new mechanically strong, highly bioactive, dilute magnesium-doped wollastonite (CaSiO3-Mg; CSi-Mg) porous scaffold by the robocasting technique. The sintered scaffolds had interconnected pores of 350 μm in size and over 50% porosity with appreciable compressive strength (>110 MPa), 5−10 times higher than those of pure CSi and β-TCP porous ceramics. ...
Free Fatty Acid Receptor 4 (GPR120) Stimulates Bone Formation and Suppresses Bone Resorption in the Presence of Elevated n-3 Fatty Acid Levels
Free fatty acid receptor 4 (FFA4) has been reported to be a receptor for n-3 fatty acids (FAs). Although n-3 FAs are beneficial for bone health, a role of FFA4 in bone metabolism has been rarely investigated. We noted that FFA4 was more abundantly expressed in both mature osteoclasts and osteoblasts than their respective precursors, and that it was activated by docosahexaenoic acid (DHA). FFA4 knockout (Ffar4-/-) and wild-type mice exhibited similar bone masses when fed on a normal diet. Since fat-1 transgenic (fat-1Tg+) mice endogenously converting n-6 to n-3 FAs contain high n-3 FA levels, we crossed Ffar4-/- and fat-1Tg+ mice over 2 generations to generate 4 genotypes of mice littermates: Ffar4+/+;fat-1Tg-, Ffar4+/+;fat-1Tg+, Ffar4-/-;fat-1Tg-, and Ffar4-/-;fat-1Tg+. ...
Bone marrow stem cells assuage radiation-induced damage in a murine model of distraction osteogenesis: A histomorphometric evaluation
The purpose of this study is to determine if intraoperatively placed bone marrow stem cells (BMSCs) will permit successful osteocyte and mature bone regeneration in an isogenic murine model of distraction osteogenesis (DO) following radiation therapy (XRT). Lewis rats were split into three groups, DO only (Control), XRT followed by DO (xDO) and XRT followed by DO with intraoperatively placed BMSCs (xDO-BMSC). Coronal sections from the distraction site were obtained, stained and analyzed via statistical analysis with analysis of variance (ANOVA) and subsequent Tukey or Games-Howell post-hoc tests. ...
Rebamipide Attenuates Mandibular Condylar Degeneration in a Murine Model of TMJ-OA by Mediating a Chondroprotective Effect and by Downregulating RANKL-Mediated Osteoclastogenesis
Authors
Takashi Izawa , Hiroki Mori, Tekehiro Shinohara, Akiko Mino-Oka, Islamy Rahma Hutami, Akihiko Iwasa, Eiji Tanaka
Abstract
Abstractemporomandibular joint osteoarthritis (TMJ-OA) is characterized by progressive degradation of cartilage and changes in subchondral bone. It is also one of the most serious subgroups of temporomandibular disorders. Rebamipide is a gastroprotective agent that is currently used for the treatment of gastritis and gastric ulcers. It scavenges reactive oxygen radicals and has exhibited anti-inflammatory potential. The aim of this study was to investigate the impact of rebamipide both in vivo and in vitro on the development of cartilage degeneration and osteoclast activity in an experimental murine model of TMJ-OA, and to explore its mode of action. Oral administration of rebamipide (0.6 mg/kg and 6 mg/kg) was initiated 24 h after TMJ-OA was induced, and was maintained daily for four weeks. Rebamipide treatment was found to attenuate cartilage degeneration, to reduce the number of apoptotic cells, and to decrease the expression levels of matrix metalloproteinase-13 (MMP-13) and inducible nitric oxide synthase (iNOS) in TMJ-OA cartilage in a dose-dependent manner. Rebamipide also suppressed the activation of transcription factors (e.g., NF-κB, NFATc1) and mitogen-activated protein kinases (MAPK) by receptor activator of nuclear factor kappa-B ligand (RANKL) to inhibit the differentiation of osteoclastic precursors, and disrupted the formation of actin rings in mature osteoclasts. Together, these results demonstrate the inhibitory effects of rebamipide on cartilage degradation in experimentally induced TMJ-OA. Furthermore, suppression of oxidative damage, restoration of extracellular matrix homeostasis of articular chondrocytes, and reduced subchondral bone loss as a result of blocked osteoclast activation suggest that rebamipide is a potential therapeutic strategy for TMJ-OA.
Link to Article
http://dx.doi.org/10.1371/journal.pone.0154107
A Comparison of Vascularity, Bone Mineral Density Distribution, and Histomorphometrics in an Isogenic Versus an Outbred Murine Model of Mandibular Distraction Osteogenesis
Authors
Edward G. Carey, Sagar S. Deshpande, Alexander R. Zheutlin, Noah S. Nelson, Alexis Donneys, Stephen Y. Kang, Kathleen K. Gallagher, Peter A. Felice, Catherine N. Tchanque-Fossuo, Steven R. Buchman
Abstract
Background
Vascularity, bone mineral density distribution, and histomorphometrics between the inbred, isogenic Lewis rat and the outbred, nonisogenic Sprague Dawley rat within mandibular distraction osteogenesis (MDO) must be compared in order for future researchers to compare results generated from these two animals. We hypothesize that little difference will be found between the two strains within these metrics.
Methods
The investigators implemented a comparative study between the Lewis and Sprague Dawley rat strains within MDO. The sample was composed of 17 male Lewis and 17 male Sprague Dawley rats, which underwent surgical external fixation and distraction. Rats’ hemimandibles were distracted to a total distance of 5.1 mm. After 28 days of consolidation, 9 rats from each group underwent bone mineral density distribution analysis. The remaining rats from each group were analyzed for vascular and histologic metrics. Descriptive and bivariate statistics were computed and the p-value was set at 0.05.
Results
We demonstrated successful mandibular distraction osteogenesis in all animals, with no significant difference found in histologic or bone mineral density distribution metrics. No significant differences were found in any of the vascular metrics, with the exception of vascular separation that was not normalized to mandibular volume (p = 0.048).
Conclusion
This study demonstrates that little dissimilarity exists between the isogenic Lewis and the outbred Sprague Dawley models of mandibular distraction osteogenesis. Given this, researchers may confidently compare gross results between the two strains while taking into consideration the very small differences between the models. For studies that require an isogenic strain, the Lewis rat is an apt surrogate for the Sprague Dawley strain.
Link to Article
http://dx.doi.org/10.1016/j.joms.2016.04.01