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Background: Osteolytic diseases such as osteoporosis are featured with accelerated osteoclast differentiation and strong bone resorption. Considering the complications and other limitations of current drug treatments, it is necessary to develop a safer and more reliable drug to deal with osteoclast-related diseases. Saikosaponin D (SSD) is the active extract of Bupleurum, which has anti-inflammation, anti-tumor and liver protection functions. However, the role of SSD in regulating the differentiation and function of osteoclasts is not clear., Purpose: To explore whether SSD could prevent osteoclast differentiation and bone resorption induced by M-CSF and RANKL, and further evaluate the potential therapeutic properties of SSD in LPS-induced inflammatory bone loss mouse models., Methods: BMMs were cultured in complete medium stimulated by RANKL with different concentrations of SSD. TRAP staining, bone resorption determination, qRT-PCR, immunofluorescence and Western blotting were performed. A mouse model of LPS-induced calvarial bone loss was established and treated with different doses of SSD. The excised calvaria bones were used for TRAP staining, micro-CT scan and histological analysis., Results: SSD inhibited the formation and bone resorption of osteoclasts induced by RANKL in vitro. SSD suppressed LPS-induced inflammatory bone loss in vivo., Conclusion: SSD inhibited osteoclastogenesis and LPS-induced osteolysis in mice both which served as a new potential agent for the treatment of osteoclast-related conditions., Competing Interests: The authors declare no conflicts of interest., (© 2021 Wu et al.)

Introduction: Osteoporosis is a metabolic bone disease characterized by reduced bone quantity and microstructure, typically owing to increased osteoclastogenesis and/or enhanced osteoclastic bone resorption, resulting in uncontrolled bone loss, which primarily affects postmenopausal women. In consideration of the severe side effects of current drugs for osteoporosis, new safe and effective medications are necessary. Pristimerin (Pri), a quinone methide triterpene extracted from Celastraceae and Hippocrateaceae members, exhibits potent antineoplastic and anti-inflammatory effects. However, its effect on osteoclasts remains unknown., Materials and Methods: We evaluated the anti-osteoclastogenic and anti-resorptive effect of Pri on bone marrow-derived osteoclasts and its underlying mechanism in vitro. In addition, the protective effect of Pri on ovariectomy model was also explored in vivo., Results: In vitro, Pri inhibited osteoclast differentiation and mature osteoclastic bone resorption in a time- and dose-dependent manner. Further, Pri suppressed the expression of osteoclast-related genes and the activation of key proteins. Pri also inhibited the early activation of ERK, JNK MAPK, and AKT signaling pathways in bone marrow-derived macrophages (BMMs), ultimately inhibiting the induction and activation of the crucial osteoclast transcriptional factor nuclear factor of activated T-cell cytoplasmic 1 (NFATc1). In vivo, consistent with our in vitro data, Pri clearly prevented ovariectomy-induced bone loss., Conclusion: Our data showed that Pri inhibits the differentiation and activation of osteoclasts in vitro and in vivo, and could be a promising candidate for treating osteoporosis., Competing Interests: The paper has been polished by a professional English native speaker. The authors declare no other potential conflicts of interest for this work., (© 2020 Sun et al.)

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 .

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., (© 2018 Wiley Periodicals, Inc.)

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]