ReferenceID 5097
Dendrobine attenuates osteoclast differentiation through modulating ROS/NFATc1/ MMP9 pathway and prevents inflammatory bone destruction
Phytomedicine
BACKGROUND: Osteolytic diseases share symptoms such as bone loss, fracture and pain, which are caused by over-activated osteoclasts. Targeting osteoclast differentiation has emerged as a therapeutic strategy clinically.
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Record Fields
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- Reference Id
- 5097
- Evidence Id
- 21687
- Core Evidence Id
- 21687
- Source Reference Id
- 3483
- Herb2 Reference Id
- HBREF004280
- Subject Paper Key
- HBIN023277_34801352
- Pubmed Id
- 34801352
- Doi
- 10.1016/j.phymed.2021.153838
- Paper Title
- Dendrobine attenuates osteoclast differentiation through modulating ROS/NFATc1/ MMP9 pathway and prevents inflammatory bone destruction
- Paper Abstract
- BACKGROUND: Osteolytic diseases share symptoms such as bone loss, fracture and pain, which are caused by over-activated osteoclasts. Targeting osteoclast differentiation has emerged as a therapeutic strategy clinically. Dendrobine is an alkaloid isolated from Chinese herb Dendrobium nobile, with knowing effects of analgesia and anti-inflammation. The roles of dendrobine on osteoclasts and osteolysis remain unclear. PURPOSE: Herein, the possible roles of dendrobine in osteoclastogenesis, inflammatory osteolysis and the underlying mechanism were explored. METHODS: Bone marrow-derived macrophages (BMMs) and RAW264.7 cells were employed to evaluate the roles of dendrobine on osteoclastogenesis, bone absorption and the underlying mechanism in vitro. LPS injection was used to cause inflammatory osteolysis in vivo. RESULTS: Dendrobine repressed osteoclastogenesis, bone resorption induced by receptor activator of nuclear factor kappa B ligand (RANKL) in vitro. Mechanistically, dendrobine inhibited RANKL-upregulated intracellular (ROS), p-p38, c-Fos expression and nuclear factor of activated T cells (NFATc1) nuclear translocation. Osteoclastic genes were reduced, and among them matrix metalloproteinase 9 (MMP9) mRNA was dramatically blocked by dendrobine. Moreover, it substantially suppressed MMP9 protein expression during osteoclastogenesis in vitro. Accordingly, oral 20 mg/kg/day dendrobine was capable of preventing LPS-induced osteolysis with decreased osteoclasts in vivo. CONCLUSION: Taken together, dendrobine suppresses osteoclastogenesis through restraining ROS, p38-c-Fos and NFATc1-MMP9 in vitro, thus attenuates inflammatory osteolysis in vivo. This finding supports the discover of dendrobine as a novel osteoclast inhibitor for impeding bone erosion in the future.
- Journal
- Phytomedicine
- Publish Year
- 2022
- Experiment Subject
- Experiment Type
- Cell Experiment
- Phenotype Related
- Bone Loss; Osteolytic Diseases; Osteolysis; Fracture And Pain; Inflammatory Osteolysis
- Paper Title Cn
- Paper Title En
- Dendrobine attenuates osteoclast differentiation through modulating ROS/NFATc1/ MMP9 pathway and prevents inflammatory bone destruction
- Bilingual Status
- semi_complete