ReferenceID 5477
Icariin ameliorates estrogen-deficiency induced bone loss by enhancing IGF-I signaling via its crosstalk with non-genomic ERα signaling
Phytomedicine
BACKGROUND: Rapid, non-genomic estrogen receptor (ER) signaling plays an integral role in mediating the tissue selective properties of ER modulators. Icariin, a bone bioactive flavonoid, has been reported to selectively
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Record Fields
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- Reference Id
- 5477
- Evidence Id
- 22067
- Core Evidence Id
- 22067
- Source Reference Id
- 4198
- Herb2 Reference Id
- HBREF004995
- Subject Paper Key
- HBIN029922_33339654
- Pubmed Id
- 33339654
- Doi
- 10.1016/j.phymed.2020.153413
- Paper Title
- Icariin ameliorates estrogen-deficiency induced bone loss by enhancing IGF-I signaling via its crosstalk with non-genomic ERα signaling
- Paper Abstract
- BACKGROUND: Rapid, non-genomic estrogen receptor (ER) signaling plays an integral role in mediating the tissue selective properties of ER modulators. Icariin, a bone bioactive flavonoid, has been reported to selectively activate non-genomic ERalpha signaling in in vitro and in vivo studies. PURPOSE: The mechanisms underlying the estrogen-like bone protective effects of icariin are not fully understood, especially those that are related to insulin-like growth factor I (IGF-1) signaling. The bone protective effects of icariin were investigated in female mature ovariectomized (OVX) rats and the signaling of IGF-IR- ERalpha cross-talk was determined in osteoblastic cells. STUDY DESIGN AND METHODS: Icariin at 3 different dosages (50, 500 and 3000 ppm) were orally administrated to rats for 3 months through daily intake of phytoestrogen-free animal diets containing icariin. Bone marrow stromal cells (BMSCs) and osteoclast precursors from femurs were harvested for experiments and RNA-sequencing. The interactions between IGF-IR and non-genomic ERalpha signaling were examined in pre-osteoblastic MC3T3-E1 cells and mature osteoblasts differentiated from BMSCs. RESULTS: Our results show that chronic administration of icariin to OVX rats significantly protected them against bone loss at the long bone and lumbar spine without inducing any uterotrophic effects. Ex vivo studies using BMSCs and osteoclast precursors confirmed the stimulatory effects of icariin on osteoblastogenesis and its inhibitory effects on osteoclastogenesis, respectively. RNA-sequencing analysis of mRNA from BMSCs revealed that icariin at 500 ppm significantly altered IGF-1 signaling as well as PI3K-Akt pathways. Our results demonstrated for the first time the rapid induction of interactions between IGF-IR and ERalpha as well as IGF-IR signaling and the downstream Akt phosphorylation by icariin in MC3T3-E1 cells. The activation of ERalpha and Akt phosphorylation by icariin in MC3T3-E1 cells and the osteogenic effects of icariin on ALP activity in mature osteoblasts were shown to be IGF-IR-dependent. CONCLUSION: Our findings reveal that icariin activates both ERalpha and Akt via enhancing rapid induction of IGF-1 signaling in osteoblastic cells for osteogenesis and might be regarded as a novel pathway-selective phytoestrogen for management of postmenopausal osteoporosis.
- Journal
- Phytomedicine
- Publish Year
- 2021
- Experiment Subject
- rat; mc3t3-e1 cells; pre-osteoblastic mc3t3-e1 cells
- Experiment Type
- Animal Experiment
- Phenotype Related
- Postmenopausal Osteoporosis
- Paper Title Cn
- Paper Title En
- Icariin ameliorates estrogen-deficiency induced bone loss by enhancing IGF-I signaling via its crosstalk with non-genomic ERα signaling
- Bilingual Status
- semi_complete