Icariin is the major active ingredient in Herba epimedii which is a commonly used Chinese herbal medicine for the treatment of osteoporosis. The present study aims to evaluate the osteoprotective effect of Icariin in glucocorticoid-induced osteoporosis in vivo and investigate the effect of Icariin on glucocorticoid-induced osteocyte apoptosis in vitro. A total of 48 female Sprague-Dawley rats were used. Glucocorticoid-induced osteoporosis was induced by daily injections of dexamethasone (0.1 mg/kg, daily, s.c.) for 60 days, whereas sham animals were injected daily with vehicle. At the end of the osteoporosis development period, osteoporotic rats were randomized to receive: vehicle (n = 8), Icariin (5,125 mg/kg, i.g.; n = 8), or alendronate (0.03 mg/kg, s.c.; n = 8) for 12 weeks. Sham animals were treated with vehicle for 12 weeks. At the beginning and at the end of treatments, animals were examined for bone mineral density. Serum bone-alkaline phosphatase and carboxy-terminal collagen cross links were measured. Primary osteocytes were isolated, and apoptosis was determined by trypan-blue assay. Interaction between Icariin and estrogen receptor and prosurvival signaling pathways activated by Icariin were also investigated. Icariin showed a comparable efficacy with alendronate in increasing bone mass. Icariin significantly increased bone-alkaline phosphatase (bone formation marker) and reduced carboxy-terminal collagen cross links (bone resorption marker). In vitro studies demonstrated that Icariin significantly prevented GC-induced apoptosis in osteocytes by activating ERK signaling via estrogen receptor. Our results suggest that Icariin might exert osteoprotective effect by maintaining osteocyte viability, thereby, regulating bone remodeling. Furthermore, our study provides preclinical evidence for the efficacy of Icariin for management of Glucocorticoid-induced osteoporosis.
Circular RNAs (circRNAs) are a novel class of noncoding RNAs that are widely expressed in human disease. However, circRNAs expression profile and potential mechanism in osteoporosis pathogenesis remain to be further studied. In the present study, a total of 69 circRNAs were identified to be abnormally expressed in osteoporosis patient samples by microarray and bioinformatics analyses. We found that circ_0011269 was notably downregulated in osteoporosis (fold change, 3.94). By means of miRanda algorithm, we constructed the interaction network of circ_0011269-miRNAs in osteoporosis based on target binding and miR-122 was enrolled in the network. Dual-luciferase reporter assay verified the target relationship of miR-122 and circ_0011269/RUNX2. The expression of circ_0011269 and RUNX2 were gradually increased during osteogenic differentiation while miR-122 exhibited a decreased expression. Moreover, overexpression of circ_0011269 could promote RUNX2 expression and inhibit osteoporosis. In summary, this study found that circ_0011269 sponges miR-122 to regulate RUNX2 expression and promotes osteoporosis progression.
BackgroundFew studies have examined the efficacy of recombinant human bone morphogenetic protein-2 (rhBMP-2) in 2-level anterior cervical discectomy and fusion (ACDF). The purpose of this study was to compare the outcomes in a series of patients with CSM treated with 2-level ACDF with or without rhBMP-2.Material/MethodsThe retrospective study included a total of 146 patients with CSM. The rhBMP-2 group consisted of 73 patients who underwent 2-level ACDF with rhBMP-2. A total of 73 patients who also received 2-level ACDF with autogenous ICBG alone were included in the matched-pair ICBG group with a ratio of 1:1, based on age, sex, and BMI. All data, including fusion rate and time, VAS, JOA score, operative date, and complications, were assessed.ResultsWith respect to the length of hospital stay, operative times, and blood loss, there were no significant difference between the 2 groups. However, the rhBMP-2 group presented a shorter fusion time (P<0.013) and higher fusion rate (P<0.036) than the ICBG group. In the rhBMP-2 group, 22% required additional treatment for complications compared to 18% of patients in the ICBG group, which showed no significant difference (P=0.543).ConclusionsThe application of rhBMP-2 in 2-level ACDF showed higher fusion rates, shorter fusion time, and similar function outcomes compared to those who received ACDF with ICBG alone.
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