Icariin ameliorates estrogen-deficiency induced bone loss by enhancing IGF-I signaling via its crosstalk with non-genomic ERα signaling |
| |
| Institution: | 1. Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong SAR;2. State Key Laboratory of Chinese Medicine and Molecular Pharmacology (Incubation), The Hong Kong Polytechnic University Shenzhen Research Institute, Shenzhen, PR China;3. Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, PR China;1. School of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510515, China;2. State Key Laboratory of Chinese Medicine and Molecular Pharmacology (Incubation), Shenzhen 518057, China;3. Integrated Hospital of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510315, China;4. Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hong Kong, China;5. Spine Disease Research Institute, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China;6. University Research Facility in Chemical and Environmental Analysis, The Hong Kong Polytechnic University, Hong Kong, China;1. Department of Joint Surgery, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, 266003, China;2. Department of Oral Implantology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, 266003, China;3. Qingdao University, Qingdao, Shandong, 266071, China;4. Medical Department of Qingdao University, Qingdao, Shandong, 266071, China |
| |
| Abstract: | BackgroundRapid, 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 ERα signaling in in vitro and in vivo studies.PurposeThe 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- ERα cross-talk was determined in osteoblastic cells.Study design and methodsIcariin 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 ERα signaling were examined in pre-osteoblastic MC3T3-E1 cells and mature osteoblasts differentiated from BMSCs.ResultsOur 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 ERα as well as IGF-IR signaling and the downstream Akt phosphorylation by icariin in MC3T3-E1 cells. The activation of ERα 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.ConclusionOur findings reveal that icariin activates both ERα 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. |
| |
| Keywords: | |
| 本文献已被 ScienceDirect 等数据库收录！ |
|
