Icariin prevents bone loss by inhibiting bone resorption and stabilizing bone biological apatite in a hindlimb suspension rodent model

Abstract

Bone loss induced by microgravity is a substantial barrier to humans in long-term spaceflight. Recent studies have revealed that icariin (ICA) can attenuate osteoporosis in postmenopausal women and ovariectomized rats. However, whether ICA can protect against microgravity-induced bone loss remains unknown. In this study, the effects of ICA on a hindlimb suspension rodent model were investigated. Two-month-old female Wistar rats were hindlimb suspended and treated with ICA (25 mg·kg·d, i.g.) or a vehicle for 4 weeks (n = 6). The bone mass density of the hindlimbs was analyzed using dual-energy X-ray absorptiometry and micro-CT. mRNA expression of osteogenic genes in the tibia and the content of bone metabolism markers in serum were measured using qRT-PCR and ELISA, respectively. The bone mineral phase was analyzed using X-ray diffraction and atomic spectrometry. The results showed that ICA treatment significantly rescued the hindlimb suspension-induced reduction in bone mineral density, trabecular number and thickness, as well as the increases in trabecular separation and the structure model index. In addition, ICA treatment recovered the decreased bone-related gene expression, including alkaline phosphatase (ALP), bone glaprotein (BGP), and osteoprotegerin/receptor activator of the NF-κB ligand ratio (OPG/RANKL), in the tibia and the decreased bone resorption marker TRACP-5b levels in serum caused by simulated microgravity. Notably, ICA treatment restored the instability of bone biological apatite and the metabolic disorder of bone mineral elicited by simulated microgravity. These results demonstrate that ICA treatment plays osteoprotective roles in bone loss induced by simulated microgravity by inhibiting bone resorption and stabilizing bone biological apatite.

Effects of Icariin on Modulating Gut Microbiota and Regulating Metabolite Alterations to Prevent Bone Loss in Ovariectomized Rat Model

“…Here, we found a great ability of ICA administration to improve the micro-architecture of bone trabecula and increase BMD and BV/TV in OVX rats ( Figure 1 ), in accordance with the recent studies from Wei et al ( 14 ) and Zhou et al ( 16 ). A significant decrease of BGP and RANK and increase of OPG in OVX rat serum suggested a direct evidence of ICA-induced osteogenic differentiation ( 38 ), which was probably mediated via Wnt/β-catenin pathway like other TCMs such as radix Salviae miltiorrhizae (RSM) and Liuwei Dihuang ( 10 , 13 , 39 , 40 ). Other signaling pathways including IGF-I coupled non-genomic ERα and STAT associated with ICA-induced OP improvement have also been documented ( 16 , 17 ), but whether the pathways RANKL/RANK/TRAF6 and OPG/RANKL/cathepsin K identified in other TCMs ( 39 , 41 ) can be activated by ICA still warrants further investigations.…”

The phytoestrogen glabrene prevents osteoporosis in ovariectomized rats through upregulation of the canonical Wnt/β‐catenin signaling pathway

“…Bone strength plays a key role in maintaining bone health, including bone density, architecture, mineralization, and load tolerance of both cortical and trabecular bone area. [ 36,37 ] Although BMD is an essential factor of bone strength, it cannot be held accountable for the architectural changes occurring in trabecular bone. [ 38,39 ] The assessment of both BMD and bone biomechanical properties may improve the estimation of bone strength.…”

Chrysophanic acid shifts the differentiation tendency of BMSCs to prevent alcohol‐induced osteonecrosis of the femoral head

“…Recently, an increasing interest has risen for the treatment of intractable bone diseases with traditional Chinese medicine (TCM) 14 . Our previous studies have indicated that muscone, cordycepin and osthole have beneficial effects for ONFH 15‐17 .…”