Jianwei Wang and Shan Tao contributed equally to this work. Rachner TD, Khosla S, Hofbauer LC. Afterwards, the Sim loaded DDSs were tested under different given drug concentration to explore the optimal concentration of Tc/ACC/Sim for osteoblast differentiation and mineralization. DENSITY 3 package. In order to find the optimized administration dosage, the cytotoxicity of drug free carriers and DDSs on MC3T3-E1 cells were investigated individually.  |  Pathogenesis of osteoporosis: concepts, conflicts, and prospects. 2011;377:1276-87, 6. Finally, the in vitro and in vivo osteoporosis reversing efficacy of Tc/ACC/Sim were investigated to confirm the promising osteoporosis therapy using synergetic calcium supplement and osteoblast promotion strategy. The bone morphogenetic proteins (BMPs)-Smad is one of the important regulatory signaling pathway responsible for the formation of bone [19]. Article can not be printed. As a service to our authors and readers, this journal provides supporting information supplied by the authors. 2013;10:4159-67, 9. Besides, all femurs were decalcified in EDTA, dehydrated, and then embedded in paraffin to obtain sections of 4 µm thickness, which were then stained with hematoxylin and eosin (HE). MC3T3-E1 cells were cultured in standard osteogenic differentiation and mineralization medium containing 10 mM β-glycerophosphate, 50 µg/mL ascorbic acid and different formulations at the equal Sim concentration of 10, Female Sprague Dawley rats were randomly selected and subjected to sham operation or bilaterally oophorectomy. Amorphous Calcium Carbonate, DENSITY KIDS 6 package. N) and separation (Tb. The drug loading content of PL/ACC/Sim and Tc/ACC/Sim were analyzed by a high-performance liquid chromatography (HPLC) with an Agilent ZORBAX SB-C18 column (4.6 mm×150 mm, 5 µm). ICG labeled PL/ACC and Tc/ACC were injected into mice through the tail vein. 2015;10:5671-85, 15. The other steps are the same as above. Choosing a selection results in a full page refresh. var thismailbody12 = "zj"; Wang C, Yu F, Liu X, Chen S, Wu R, Zhao R. et al. thismailbody3 = thismailbody3+"2e;"; var thismailbody2 = ""; 2018;10:25547-60, 43. In particular, the combination of calcium supplement and osteoblasts promotion using ACC and Sim (PL/ACC/Sim and Tc/ACC/Sim) showed further enhanced benefits on osteoblast mineralization. Briefly, SA (213 mg), EDC (216 mg) and HOBT (150 mg) at the mol ratio of 1:1.5:1.5 (SA: EDC: HOBT) were co-dissolved in 30 mL anhydrous DMF. DENSITY 9 package. All authors have given approval to the final version of the manuscript. Female Sprague Dawley rats were randomly selected and subjected to sham operation or bilaterally oophorectomy. We firstly evaluated the toxicity of the constructed nanocarriers (PL/ACC and Tc/ACC) to cells using MTT method. Because of that, it is recommended to add Density, the Amorphous Calcium carbonate. NIH All animal experiments were approved by the Animal Care and Use Committee of Zhejiang University in accordance with the guidelines for the care and use of laboratory animals. Keywords: Find NCBI SARS-CoV-2 literature, sequence, and clinical content: https://www.ncbi.nlm.nih.gov/sars-cov-2/. Sim has the potential to increase BMP-2 expression and promote the formation of new bone in vitro. MC3T3-E1 cells were seeded at 1×104 cells/well in 96-well plates and incubated for 24 h, after which cells were exposed to a series of concentrations of PL/ACC, Tc/ACC, Sim, PL/ACC/Sim and Tc/ACC/Sim for 48 h, after which 20 µL of 5 mg/mL MTT was added to each well for another 4 h followed by adding 200 µL of DMSO into each well to dissolve the forming formazan crystals. In the end, the ODA-FITC was dried at room temperature and stored in the dark. Bone-targeted delivery of simvastatin-loaded PEG-PLGA micelles conjugated with tetracycline for osteoporosis treatment. In clinical and pre-clinical studies, we found that the ACC is 120 times more soluble and absorbed twice as much than the Crystalline Calcium Carbonate (CCC). Alpha-minimum essential medium (αMEM) was from Thermo-Fisher Scientific (Waltham, MA, USA). Enter your email address below and we will send you your username, If the address matches an existing account you will receive an email with instructions to retrieve your username, By continuing to browse this site, you agree to its use of cookies as described in our, I have read and accept the Wiley Online Library Terms and Conditions of Use, anie201602849-sup-0001-misc_information.pdf. Th and Tb. It is also noted that the Tc/ACC/Sim treated group showed more resemblance to the SHAM group. The company deals only with high efficiency premium products. 1965;208:787-8, 16. Density is our Amorphous Calcium Carbonate (ACC). The Lancet. Cancer-Specific Therapy by Artificial Modulation of Intracellular Calcium Concentration. Scale bar: 100 nm. 2019;9:1125, 38. Indocyanine green (ICG) was purchased from Molecular Probes (Eugene, OR, USA). In addition, it was generally recognized that the osteoclast activation is usually associated with the release of phosphate radicals, which gradually develops an acidic microenvironment within the osteoporosis lesions [12, 13]. Scale bar: 100 nm. In addition, in vitro and in vivo osteoporosis reversing assays demonstrated beneficial effects of mono therapy using either calcium supplement or Sim induced osteoblast promotion. and you may need to create a new Wiley Online Library account. Corresponding authors: E-mails: 11519016 thismailbody3 = thismailbody1; MC3T3-E1 cells were incubated with ODA-FITC labeled PL/ACC and Tc/ACC for different time intervals (2, 4, 6, 10 h) and then subjected to observation using confocal microscope. 81773644) and Natural Science Foundation of Zhejiang Province (No.


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