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Research on implementing task-based language-teaching (TBLT) shows that adapting TBLT in ways that are inconsistent with its principles is common among nonnative-speaker English-as-a-foreign-language teachers. Our study of Canadian native-speaker English-as-a-second language teachers reveals how they also adapt TBLT in ways that are incongruent with its theoretical underpinnings, turning it into Presentation-Practice-Production. We thus question speaker identity as an indicator of a teacher's propensity to adapt TBLT and call for professional development on the effective practice of TBLT for all English-language teachers regardless of their speaker identities.

Osteoarthritis (OA) is the most common joint disease in the elderly, characterized by cartilage degradation and proliferation of subchondral bone. The pathogenesis of OA involves a variety of inflammatory mediators, including nitric oxide (NO), prostaglandin E2 (PGE2), tumor necrosis factor (TNF)-α, and interleukin (IL)-1β. From the molecular mechanism, the nuclear factor-erythroid 2-related factor (Nrf2)/heme oxygenase-1 (HO-1) pathway and the expression of ROS regulated the production of the above inflammatory mediators. Saikosaponin D (SSD), which is an active ingredient isolated from Bupleurum, has various biological functions. In this study, IL-1β was used as a pro-inflammatory factor to create an in vitro OA model. According to the results of high-density culture, qPCR, ROS measurement, Western blot, and immunofluorescence, SSD activated the Nrf2/HO-1/ROS axis, inhibited the production of inflammatory mediators, and protected against ECM destruction. The DMM mouse model was used as a model of OA in mice. From the results of safranin O/fast green staining, hematoxylin–eosin staining, tartrate-resistant acid phosphatase (TRAP) staining, and OARSI scores, SSD protected against the mice knee articular cartilage degeneration and reduced the number of osteoclasts in the subchondral bone. Experimental results found that SSD suppressed IL-1β–induced differentiated ATDC 5 chondrocytes apoptosis via the Nrf2/HO-1/ROS axis in vitro. SSD delayed the progression of OA in DMMs model mice in vivo. Therefore, SSD has the potential to become a drug for clinical treatment of OA. [ABSTRACT FROM AUTHOR]

Osteolytic diseases are characterized by an increase in the number and/or activity of bone‐resorbing osteoclasts. Identification of natural compounds that can suppress osteoclast formation and function is crucial for the prevention and treatment of osteolytic diseases. Vitexin, a naturally‐derived flavonoid extracted from various medicinal plant species, demonstrates a broad range of pharmacological properties including anticancer and anti‐inflammatory effects. Here in this study, we showed that vitexin exerts antiosteoclastogenic effects by directly inhibiting receptor activator of nuclear factor‐κB ligand (RANKL)‐induced osteoclast formation and bone resorption in vitro and protected against lipopolysaccharide (LPS)‐induced inflammatory osteolysis in vivo. Vitexin suppressed the early activation of ERK and p38 MAPK pathways in response to RANKL thereby attenuating the downstream induction of c‐Fos and NFATc1, and abrogating the expression of osteoclast marker genes. Collectively, these results provide evidence for the therapeutic application of vitexin in the treatment of osteoclast‐mediated bone lytic diseases. [ABSTRACT FROM AUTHOR]

Osteoclasts (OCs) are multinuclear giant cells responsible for bone resorption, and an excessive bone resorption by OCs plays an important role in osteoporosis. Commonly used drugs for the treatment of osteoporosis have severe side effects. As such, identification of alternative treatments is essential. Garcinol, a polyisoprenylated benzophenone extracted from the fruit of Garcinia indica, has shown a strong antitumor effect through the nuclear factor‐κB (NF‐κB) and mitogen‐associated protein kinases (MAPK) signaling pathways. However, the role of garcinol in the osteoclastogenesis is still unclear. Here, we demonstrated that garcinol can inhibit the receptor activator of NF‐κB ligand (RANKL)‐induced osteoclastogenesis, osteoclastogenesis‐related gene expression, the f‐actin ring, and resorption pit formation. In addition, garcinol abrogated RANKL‐induced osteoclastogenesis by attenuating the degradation of the MAPK, NF‐κB, and PI3K‐AKT signaling pathway as well as downstream factors c‐jun, c‐fos, and NFATC1. In vivo, suppression of osteoclastogenesis by garcinol was evidenced by marked inhibition of lipopolysaccharide‐induced bone resorption. In conclusion, our data demonstrated that garcinol inhibited the RANKL‐induced osteoclastogenesis by suppressing the MAPK, NF‐κB, and PI3K‐AKT signaling pathways and thus has potential as a novel therapeutic option for osteolytic bone diseases. Garcinol suppresses osteoclast (OCs) formation and function in vitro. Garcinol impairs the receptor activator for the nuclear factor‐κB ligand (RANKL)‐induced mitogen‐associated protein kinases (MAPK), nuclear factor‐κB (NF‐κB), and AKT signaling pathway. Garcinol suppresses osteolysis in vivo. Garcinol may be a new therapeutic option for osteolytic bone diseases [ABSTRACT FROM AUTHOR]

Excessive bone resorption by osteoclasts (OCs) plays an important role in lytic bone diseases, such as osteoporosis. Although the pharmacological treatment of osteoporosis has been extensively developed, alternative treatments are still needed. Deguelin, a rotenoid isolated from several plant species, is a strong antitumor agent; however, its effect on OCs remains unclear. To the best of our knowledge, this is the first study to report that deguelin inhibits the receptor activator of nuclear factor‐κB (NF‐κB) ligand (RANKL)‐induced osteoclastogenesis, messenger RNA expression of osteoclastic‐specific genes, and osteoclastic bone resorption, in primary bone marrow‐derived macrophages. At the molecular level, deguelin markedly blocked RANKL‐induced osteoclastogenesis by attenuating the phosphorylation of NF‐κB p65 and inhibiting p65 nuclear translocation. In addition, deguelin suppressed the downstream expression of nuclear factor of activated T‐cell cytoplasmic 1, which is a crucial transcription factor in OC differentiation. Consistent with the in vitro results, deguelin inhibited lipopolysaccharide‐induced bone resorption by suppressing osteoclastogenesis. Taken together, our findings reveal that deguelin has antiosteoclastic effects in vitro and in vivo and possesses potential as a new therapeutic option for osteolytic bone diseases. Deguelin suppresses osteoclast formation and function in vitro. Deguelin impairs the receptor activator of nuclear factor‐κB (NF‐κB) ligand (RANKL)‐induced NF‐κB signaling pathway. Deguelin suppresses osteolysis in vivo. Deguelin may be used for treating osteoclast‐related diseases. [ABSTRACT FROM AUTHOR]

Excessive alcohol consumption is positively related to osteoporosis, and its treatment strategies are poorly developed. Disulfiram inhibits receptor activator of nuclear factor kappa-B ligand (RANKL)-induced osteoclastogenesis; however, whether it can be used for ethanol-induced osteoclastogenesis and its underlying mechanism are still unclear. In this study, we demonstrated that ethanol promoted RANKL-induced osteoclast formation and bone resorption, whereas, disulfiram suppressed ethanol-induced osteoclastogenesis by abrogating the expression of nuclear factor of activated T cell c1 (NFATc1) in vitro. Further analysis revealed that aldehyde dehydrogenase 1A1 (ALDH1A1) is important for the expression of NFATc1, the master regulator of osteoclast differentiation. Furthermore, we showed that disulfiram protected ethanol-induced osteoporosis in vivo. Overall, our study provides promising evidence that disulfiram can be used as a treatment strategy for alcohol-related osteoporosis via the ALDH1A1T-NFATc1 axis.

Postmenopausal osteoporosis is the most common form of primary osteoporosis, and the incidence of the condition is rapidly increasing. In consideration of the limitations of current therapeutic options for the treatment of postmenopausal osteoporosis, there is an urgent need to develop safer alternatives. Anacardic acid, a natural phenolic acid compound extracted from cashew nut shell, possesses potent antitumor and anti-inflammatory effects and inhibits NF-κB signaling. However, its effect on osteoclasts remains unknown. This study reports the first evidence for the antiosteoclastogenic and antiresorptive effects of anacardic acid on bone marrow-derived macrophage-derived osteoclasts. Mechanistically, anacardic acid disrupts the phosphorylation of TGF-β activated kinase 1 and subsequently suppresses multiple receptor activator of NF-κB ligand-induced signaling cascades, ultimately inhibiting the induction and activation of the crucial osteoclast transcriptional factor nuclear factor of activated T-cell cytoplasmic 1. Consistent with cellular results in vitro , anacardic acid treatment improves bone density in the murine model of ovariectomy-induced bone loss. Taken together, our study provides promising evidence for the therapeutic application of anacardic acid as a new potential pharmacological treatment for osteoporosis.-Zhao, K., Jia, Y., Peng, J., Pang, C., Zhang, T., Han, W., Jiang, J., Lu, X., Zhu, J., Qian, Y. Anacardic acid inhibits RANKL-induced osteoclastogenesis in vitro and prevents ovariectomy-induced bone loss in vivo .

Bone fracture healing is a complex, dynamic process that involves various cell types, with osteoclasts and osteoblasts playing indispensable roles. In this study, we found that psoralen, the main active ingredient in Psoralea corylifolia L. fruit extract, enhanced bone fracture healing through activation of osteoclast and osteoblast activity via the ERK signaling pathway. In detail, psoralen promoted receptor activator of nuclear factor-κB ligand-induced osteoclastogenesis, mRNA expression of osteoclast-specific genes, and osteoclastic bone resorption in primary bone marrow-derived macrophages. Meanwhile, psoralen induced osteogenic differentiation by promoting the mRNA expression of the osteoblast differentiation markers alkaline phosphatase, runt-related transcription factor 2, osterix, and osteocalcin. At the molecular level, psoralen preferentially activated ERK1/2 but not JNK or p38 MAPKs. Further experiments revealed that psoralen-induced osteoclast and osteoblast differentiation was abrogated by a specific inhibitor of phosphorylated ERK. In addition, psoralen accelerated bone fracture healing in a rat tibial fracture model, and the numbers of osteoclasts and osteoblasts were increased in psoralen-treated fracture callus. Taken together, our findings indicate that psoralen accelerates bone fracture healing through activation of osteoclasts and osteoblasts via ERK signaling and has potential as a novel drug in the orthopedic clinic for the treatment of bone fractures.-Zhang, T., Han, W., Zhao, K., Yang, W., Lu, X., Jia, Y., Qin, A., Qian, Y. Psoralen accelerates bone fracture healing by activating both osteoclasts and osteoblasts.