N,N-Dimethylformamide inhibits high glucose-induced osteoporosis via attenuating MAPK and NF-κB signalling

Liu, Ya Dong; Liu, Jianfeng; Liu, Bin

doi:10.1302/2046-3758.114.bjr-2020-0308.r2

Cited by 11 publications

(6 citation statements)

References 60 publications

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“…MAPK family proteins are key signalling proteins, 49 and MAPK-p38 is closely related to cell differentiation and apoptosis. 50 , 51 In eukaryotic cells, the MAPK signal cascade is the most conserved and well-studied signal transduction system. Classic MAPK cascade transduction is activated by a three-stage kinase cascade.…”

Section: Discussionmentioning

confidence: 99%

Melatonin induces RAW264.7 cell apoptosis via the BMAL1/ROS/MAPK-p38 pathway to improve postmenopausal osteoporosis

Wang,

Jiang,

Pan

et al. 2023

Bone Joint Res

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AimsCurrently, the effect of drug treatment for osteoporosis is relatively poor, and the side effects are numerous and serious. Melatonin is a potential drug to improve bone mass in postmenopausal women. Unfortunately, the mechanism by which melatonin improves bone metabolism remains unclear. The aim of this study was to further investigate the potential mechanism of melatonin in the treatment of osteoporosis.MethodsThe effects of melatonin on mitochondrial apoptosis protein, bmal1 gene, and related pathway proteins of RAW264.7 (mouse mononuclear macrophage leukaemia cells) were analyzed by western blot. Cell Counting Kit-8 was used to evaluate the effect of melatonin on cell viability. Flow cytometry was used to evaluate the effect of melatonin on the apoptosis of RAW264.7 cells and mitochondrial membrane potential. A reactive oxygen species (ROS) detection kit was used to evaluate the level of ROS in osteoclast precursors. We used bmal1-small interfering RNAs (siRNAs) to downregulate the Bmal1 gene. We established a postmenopausal mouse model and verified the effect of melatonin on the bone mass of postmenopausal osteoporosis in mice via micro-CT. Bmal1 lentiviral activation particles were used to establish an in vitro model of overexpression of the bmal1 gene.ResultsMelatonin promoted apoptosis of RAW264.7 cells and increased the expression of BMAL1 to inhibit the activation of ROS and phosphorylation of mitogen-activated protein kinase (MAPK)-p38. Silencing the bmal1 gene weakened the above effects of melatonin. After that, we used dehydrocorydaline (DHC) to enhance the activation of MAPK-p38, and the effects of melatonin on reducing ROS levels and promoting apoptosis of RAW264.7 cells were also blocked. Then, we constructed a mouse model of postmenopausal osteoporosis and administered melatonin. The results showed that melatonin improves bone loss in ovariectomized mice. Finally, we established a model of overexpression of the bmal1 gene, and these results suggest that the bmal1 gene can regulate ROS activity and change the level of the MAPK-p38 signalling pathway.ConclusionOur study confirmed that melatonin promotes the apoptosis of RAW264.7 cells through BMAL1/ROS/MAPK-p38, and revealed the therapeutic effect and mechanism of melatonin in postmenopausal osteoporosis. This finding enriches BMAL1 as a potential target for the treatment of osteoporosis and the pathogenesis of postmenopausal osteoporosis.Cite this article: Bone Joint Res 2023;12(11):677–690.

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Section: Discussionmentioning

confidence: 99%

Melatonin induces RAW264.7 cell apoptosis via the BMAL1/ROS/MAPK-p38 pathway to improve postmenopausal osteoporosis

Wang,

Jiang,

Pan

et al. 2023

Bone Joint Res

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“…The cytotoxicity of cilengitide to BMMs was determined by CCK8 method [ 25 ]. BMMs were incubated overnight, subsequently, the cells were treated with medium containing various doses of cilengitide at different time points.…”

Section: Methodsmentioning

confidence: 99%

Cilengitide inhibits osteoclast adhesion through blocking the αvβ3-mediated FAK/Src signaling pathway

Guo

Chen

et al. 2023

Heliyon

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“…Chronic inflammation is associated with numerous orthopaedic conditions including osteoarthritis (OA), rheumatoid arthritis (RA), ankylosing spondylitis, osteonecrosis, osteoporosis, and delayed and nonunion of fractures. [1][2][3][4][5][6][7][8] Transcription factor nuclear factor kappa B (NF-κB) regulates key genes involved in chronic inflammation, 9,10 and the NF-κB signalling pathway has been regarded as a potent therapeutic target for chronic inflammation. [11][12][13] The NF-κB decoy oligodeoxynucleotides (ODN) are one of the candidates for clinical application that directly prevent the binding of NF-κB to the promoter regions of targeted genes, leading to the attenuation of gene activation.…”

Section: Introductionmentioning

confidence: 99%

Sex differences of NF-κB-targeted therapy for mitigating osteoporosis associated with chronic inflammation of bone

Toya,

Kushioka,

Shen

et al. 2024

Bone Joint Res

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AimsTranscription factor nuclear factor kappa B (NF-κB) plays a major role in the pathogenesis of chronic inflammatory diseases in all organ systems. Despite its importance, NF-κB targeted drug therapy to mitigate chronic inflammation has had limited success in preclinical studies. We hypothesized that sex differences affect the response to NF-κB treatment during chronic inflammation in bone. This study investigated the therapeutic effects of NF-κB decoy oligodeoxynucleotides (ODN) during chronic inflammation in male and female mice.MethodsWe used a murine model of chronic inflammation induced by continuous intramedullary delivery of lipopolysaccharide-contaminated polyethylene particles (cPE) using an osmotic pump. Specimens were evaluated using micro-CT and histomorphometric analyses. Sex-specific osteogenic and osteoclastic differentiation potentials were also investigated in vitro, including alkaline phosphatase, Alizarin Red, tartrate-resistant acid phosphatase staining, and gene expression using reverse transcription polymerase chain reaction (RT-PCR).ResultsLocal delivery of NF-κB decoy ODN in vivo increased osteogenesis in males, but not females, in the presence of chronic inflammation induced by cPE. Bone resorption activity was decreased in both sexes. In vitro osteogenic and osteoclastic differentiation assays during inflammatory conditions did not reveal differences among the groups. Receptor activator of nuclear factor kappa Β ligand (Rankl) gene expression by osteoblasts was significantly decreased only in males when treated with ODN.ConclusionWe demonstrated that NF-κB decoy ODN increased osteogenesis in male mice and decreased bone resorption activity in both sexes in preclinical models of chronic inflammation. NF-κB signalling could be a therapeutic target for chronic inflammatory diseases involving bone, especially in males.Cite this article: Bone Joint Res 2024;13(1):28–39.

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N,N-Dimethylformamide inhibits high glucose-induced osteoporosis via attenuating MAPK and NF-κB signalling

Cited by 11 publications

References 60 publications

Melatonin induces RAW264.7 cell apoptosis via the BMAL1/ROS/MAPK-p38 pathway to improve postmenopausal osteoporosis

Melatonin induces RAW264.7 cell apoptosis via the BMAL1/ROS/MAPK-p38 pathway to improve postmenopausal osteoporosis

Cilengitide inhibits osteoclast adhesion through blocking the αvβ3-mediated FAK/Src signaling pathway

Sex differences of NF-κB-targeted therapy for mitigating osteoporosis associated with chronic inflammation of bone

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