ReferenceID 4730
Betulinic Acid Protects From Bone Loss in Ovariectomized Mice and Suppresses RANKL-Associated Osteoclastogenesis by Inhibiting the MAPK and NFATc1 Pathways
Front Pharmacol
Osteoclasts with elevated bone resorption are commonly present in postmenopausal osteoporosis, and other osteolytic pathologies. Therefore, suppressing osteoclast generation and function has been the main focus of osteop
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Record Fields
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- Reference Id
- 4730
- Evidence Id
- 21320
- Core Evidence Id
- 21320
- Source Reference Id
- 2706
- Herb2 Reference Id
- HBREF003503
- Subject Paper Key
- HBIN018373_32733253
- Pubmed Id
- 32733253
- Doi
- 10.3389/fphar.2020.01025
- Paper Title
- Betulinic Acid Protects From Bone Loss in Ovariectomized Mice and Suppresses RANKL-Associated Osteoclastogenesis by Inhibiting the MAPK and NFATc1 Pathways
- Paper Abstract
- Osteoclasts with elevated bone resorption are commonly present in postmenopausal osteoporosis, and other osteolytic pathologies. Therefore, suppressing osteoclast generation and function has been the main focus of osteoporosis treatment. Betulinic acid (BA) represents a triterpenoid mainly purified from the bark of Betulaceae. BA shows multiple biological activities, including antitumor and anti-HIV properties, but its effect on osteolytic conditions is unknown. Here, BA suppressed receptor activator of nuclear factor-kappaB ligand (RANKL)-associated osteoclastogenesis and bone resorptive function, as assessed by tartrate-resistant acid phosphatase (TRAP) staining, fibrous actin ring generation, and hydroxyapatite resorption assays. Mechanistically, BA downregulated the expression of osteoclastic-specific genes. Western blot analysis revealed that BA significantly interrupted ERK, JNK and p38 MAPK activation as well as intracellular reactive oxygen species (ROS) production, thus altering c-Fos and NFATc1 activation. Corroborating the above findings in cell-based assays, BA prevented ovariectomy-associated bone loss in an animal model. In conclusion, these findings suggest that BA can inhibit osteoclast generation and function as well as the RANKL signaling pathway, and might be used for treating osteoclast-related osteoporosis.
- Journal
- Front Pharmacol
- Publish Year
- 2020
- Experiment Subject
- Experiment Type
- Animal Experiment
- Phenotype Related
- Osteoporosis; Postmenopausal Osteoporosis; Osteoclast-related Osteoporosis; Osteolytic Conditions; Osteolytic Pathologies
- Paper Title Cn
- Paper Title En
- Betulinic Acid Protects From Bone Loss in Ovariectomized Mice and Suppresses RANKL-Associated Osteoclastogenesis by Inhibiting the MAPK and NFATc1 Pathways
- Bilingual Status
- semi_complete