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Updated: Dec 21, 2025

A RANKL-based Osteoclast Culture Assay of Mouse Bone Marrow to Investigate the Role of mTORC1 in Osteoclast Formation
Published on: March 15, 2018
Isoalantolactone inhibits RANKL-induced osteoclast formation via multiple signaling pathways
Jinwei Lu1, Zhihui Kuang1, Tao Chen1
1Department of Orthopedic Surgery, The Second Affiliated Hospital, School of Medicine, Zhejiang University, No. 88, Jiefang Road, Hangzhou 310009, China; Orthopedics Research Institute of Zhejiang University, No. 88, Jiefang Road, Hangzhou 310009, China.
Abstract:
The metabolicosteopathy known as postmenopausal osteoporosisiscaused by disruption of the balance between bone resorption and osteogenesis, processes that are mediated by osteoclasts and osteoblasts, respectively. The current therapeutic approaches to treating osteoporosis have several limitations. In this study, we demonstrated that the natural chemical compound isoalantolactone (IAL) could inhibit osteoclastogenesis, without affecting osteogenesis. This is the first study reporting a role of IAL in suppressing the receptor activator of nuclear factor-kappa B ligand (RANKL)-induced osteoclast formation in a dose-dependent manner, and downregulating the expression of osteoclast-related marker genes. Furthermore, IAL abrogated the phosphorylation of c-Jun N-terminal kinase (JNK)/p38, NF-κB, and phosphatidylinositol 3-kinase (PI3K)-AKT, and also diminished the expression of osteoclastogenesis-related proteins. In conclusion, our results indicated that IAL has promise for the treatment of osteoporosis and other metabolicbone diseases.
Insights
Isoalantolactone (IAL) shows promise for treating postmenopausal osteoporosis by inhibiting bone-resorbing osteoclasts without affecting bone-building osteoblasts. This natural compound offers a potential new therapeutic avenue for metabolic bone diseases.
Area of Science:
- Biochemistry
- Cell Biology
- Pharmacology
Background:
- Postmenopausal osteoporosis results from imbalanced bone resorption and osteogenesis.
- Current osteoporosis treatments have limitations.
Purpose of the Study:
- To investigate the effect of isoalantolactone (IAL) on osteoclastogenesis and osteogenesis.
- To explore IAL's potential as a therapeutic agent for osteoporosis.
Main Methods:
- Investigated IAL's effect on receptor activator of nuclear factor-kappa B ligand (RANKL)-induced osteoclast formation.
- Assessed IAL's impact on osteoclast-related marker gene expression.
- Analyzed IAL's effect on signaling pathways (JNK/p38, NF-κB, PI3K-AKT) and protein expression.
Main Results:
- IAL dose-dependently inhibited RANKL-induced osteoclast formation.
- IAL downregulated osteoclast-related marker genes without affecting osteogenesis.
- IAL abrogated key signaling pathway phosphorylation and reduced osteoclastogenesis-related proteins.
Conclusions:
- IAL effectively suppresses osteoclastogenesis, indicating its therapeutic potential for osteoporosis.
- IAL represents a promising natural compound for treating metabolic bone diseases.
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