ReferenceID 6432
Trilobatin ameliorates bone loss via suppression of osteoclast cell differentiation and bone resorptive function in vitro and in vivo
Life Sci
AIM: Due to on-going safety concerns or lack of efficacy of currently used medications for the treatment of osteoporosis (OP), identifying new therapeutic agents is an important part of research. In the present study, po
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Record Fields
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- Reference Id
- 6432
- Evidence Id
- 23022
- Core Evidence Id
- 23022
- Source Reference Id
- 6143
- Herb2 Reference Id
- HBREF006940
- Subject Paper Key
- HBIN047106_33497739
- Pubmed Id
- 33497739
- Doi
- 10.1016/j.lfs.2021.119074
- Paper Title
- Trilobatin ameliorates bone loss via suppression of osteoclast cell differentiation and bone resorptive function in vitro and in vivo
- Paper Abstract
- AIM: Due to on-going safety concerns or lack of efficacy of currently used medications for the treatment of osteoporosis (OP), identifying new therapeutic agents is an important part of research. In the present study, potential anti-osteoporotic activity of a natural flavonoid glycoside, trilobatin (phloretin 4-O-glucoside, Tri) was evaluated. MATERIAL AND METHODS: Osteoclastic cells were established by treating the RAW264.7 macrophage cells with RANKL and ovariectomized (OVX) C57BL/6 female mice were used as an animal model of postmenopausal OP. Actin ring formation, expression levels of osteoclastogenic marker genes and bone resorptive proteins were measured by RT-PCR, western blot, or fluorometric assays. Bone mineral density (BMD) was determined by pDEXA densitometric measurement and serum osteoprotegerin (OPG) and RANKL were measured by ELISA. KEY FINDING: Tri (5-20 muM) significantly inhibited osteoclast formation and actin ring formation in RANKL-induced osteoclasts. Tri attenuated expression of osteoclastogenic genes (MMP-9 and cathepsin K), bone resorptive proteins (CA II and integrin beta3), and osteoclastogenic signalling proteins (TRAF6, p-Pyk2, c-Cbl, and c-Src). Oral administration of Tri to OVX mice augmented BMD and serum OPG/RANKL ratio. Interestingly, while Tri and phloretin aglycone (Phl) showed similar levels of in vitro anti-osteoclastogenic activity, Tri more potently ameliorated bone loss than Phl in OVX mice. SIGNIFICANCE: This study demonstrated that Tri inhibits osteoclastic cell differentiation and bone resorption by down-regulating the expression of osteoclastogenic marker genes and signalling proteins, bone resorptive proteins, and by augmenting serum OPG/RANKL ratio, suggesting that Tri can be a novel anti-osteoporotic compound for treating senile and postmenopausal OP.
- Journal
- Life Sci
- Publish Year
- 2021
- Experiment Subject
- mouse; raw264.7 macrophage cells
- Experiment Type
- Animal Experiment
- Phenotype Related
- Osteoporosis; Senile And Postmenopausal Op; Postmenopausal Op
- Paper Title Cn
- Paper Title En
- Trilobatin ameliorates bone loss via suppression of osteoclast cell differentiation and bone resorptive function in vitro and in vivo
- Bilingual Status
- semi_complete