Artemether attenuates LPS-induced inflammatory bone loss by inhibiting osteoclastogenesis and bone resorption via suppression of MAPK signaling pathway

Liang

J of Cellular Biochemistry

et al. 2018

Osteoclasts are multinuclear giant cells responsible for bone resorption in bone loss diseases, including rheumatoid arthritis, periodontitis, and the aseptic loosening of orthopedic implants. Because of injurious side effects with currently available drugs, it is necessary to continue research novel bone‐protective therapies. Daidzin, a naturally occurring isoflavone found in leguminous plants, has numerous beneficial pharmacologic effects, including anti‐cancer, anti‐cholesterol, and anti‐angiocardiopathy, promoting osteoblasts differentiation, and even anti‐osteoporosis. However, the effect of daidzin on the regulation of osteoclast activity has not yet been investigated. In this study, our study showed that daidzin significantly inhibited receptor activator of nuclear factor‐kB ligand (RANKL)‐induced osteoclast differentiation of bone marrow macrophages and the hydroxyapatite‐resorbing activity of mature osteoclasts by inhibiting RANKL‐induced NF‐kB signaling pathway. In addition, daidzin could inhibit the expression of osteoclast marker genes, including nuclear factor of activated T cells cytoplasmic 1 (NFATc1), cellular oncogene fos (c‐Fos), tartrate‐resistant acid phosphatase (TRAP), and cathepsin K (CTSK). Consistent with in vitro results, daidzin inhibited lipopolysaccharide‐induced bone loss by suppressing the osteoclast differentiation. Together our data demonstrated that daidzin inhibits RANKL‐induced osteoclastogenesis through suppressing NF‐ĸB signaling pathway and that daidzin is a promising agent in the treatment of osteolytic diseases.

Section: Discussionmentioning

confidence: 99%

Retracted: Daidzin inhibits RANKL‐induced osteoclastogenesis in vitro and prevents LPS‐induced bone loss in vivo

Liang

J of Cellular Biochemistry

et al. 2018

J Cellular Molecular Medi

“…Subsequently, mature osteoclasts undergo polarization and structural changes to produce a tight sealing zone. Secretion of acids and proteolytic enzymes into this sealing zone results in the dissolution and degradation of the underlying bone …”

Section: Introductionmentioning

confidence: 99%

“…Several recent studies have focused on natural compounds because of their pharmacological activity against human diseases. Over several years, our group has screened natural compounds for treating osteoclast‐related diseases . Stachydrine (STA), a bioactive constituent extracted from a medicinal herb Leonurus heterophyllus Sweet, has extensive pharmacological properties, including antioxidant, anti‐inflammatory, anticancer and cardioprotective properties .…”

Section: Introductionmentioning

confidence: 99%

Stachydrine prevents LPS‐induced bone loss by inhibiting osteoclastogenesis via NF‐κB and Akt signalling

Meng

Zhou

Zhang

et al. 2019

Self Cite

Osteoclast overactivation‐induced imbalance in bone remodelling leads to pathological bone destruction, which is a characteristic of many osteolytic diseases such as rheumatoid arthritis, osteoporosis, periprosthetic osteolysis and periodontitis. Natural compounds that suppress osteoclast formation and function have therapeutic potential for treating these diseases. Stachydrine (STA) is a bioactive alkaloid isolated from Leonurus heterophyllus Sweet and possesses antioxidant, anti‐inflammatory, anticancer and cardioprotective properties. However, its effects on osteoclast formation and function have been rarely described. In the present study, we found that STA suppressed receptor activator of nuclear factor‐κB (NF‐κB) ligand (RANKL)‐induced osteoclast formation and bone resorption, and reduced osteoclast‐related gene expression in vitro. Mechanistically, STA inhibited RANKL‐induced activation of NF‐κB and Akt signalling, thus suppressing nuclear factor of activated T cells c1 induction and nuclear translocation. In addition, STA alleviated bone loss and reduced osteoclast number in a murine model of LPS‐induced inflammatory bone loss. STA also inhibited the activities of NF‐κB and NFATc1 in vivo. Together, these results suggest that STA effectively inhibits osteoclastogenesis both in vitro and in vivo and therefore is a potential option for treating osteoclast‐related diseases.

“…U0126 also suppressed osteogenesis and p‐ERK activation in MC3T3‐E1 cells induced by psoralen. In previous studies, ERK signaling activation played a critical role in osteoclast (47, 48) as well as osteoblast differentiation (49, 50). Collectively, our findings highlight the importance of ERK signaling in osteoclastogenesis and osteoblast differentiation.…”

Section: Discussionmentioning

confidence: 91%

Psoralen accelerates bone fracture healing by activating both osteoclasts and osteoblasts

et al. 2019

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. FASEB J. 33, 5399–5410 (2019). http://www.fasebj.org