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An amendment to this paper has been published and can be accessed via the original article.
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BACKGROUND: Prevalence of osteoporosis is rapidly growing and so searching for novel therapeutics. Yet, there is no drug on the market available to modulate osteoclasts and osteoblasts activity simultaneously. Thus in presented research we decided to fabricate nanocomposite able to: (i) enhance osteogenic differentiation of osteoblast, (i) reduce osteoclasts activity and (iii) reduce pro-inflammatory microenvironment. As a consequence we expect that fabricated material will be able to inhibit bone loss during osteoporosis. RESULTS: The α-Fe2O3/γ-Fe2O3 nanocomposite (IOs) was prepared using the modified sol-gel method. The structural properties, size, morphology and Zeta-potential of the particles were studied by means of XRPD (X-ray powder diffraction), SEM (Scanning Electron Microscopy), PALS and DLS techniques. The identification of both phases was checked by the use of Raman spectroscopy and Mössbauer measurement. Moreover, the magnetic properties of the obtained IOs nanoparticles were determined. Then biological properties of material were investigated with osteoblast (MC3T3), osteoclasts (4B12) and macrophages (RAW 264.7) in the presence or absence of magnetic field, using confocal microscope, RT-qPCR, western blot and cell analyser. Here we have found that fabricated IOs: (i) do not elicit immune response; (ii) reduce inflammation; (iii) enhance osteogenic differentiation of osteoblasts; (iv) modulates integrin expression and (v) triggers apoptosis of osteoclasts. CONCLUSION: Fabricated by our group α-Fe2O3/γ-Fe2O3 nanocomposite may become an justified and effective therapeutic intervention during osteoporosis treatment.
Assuntos
Anti-Inflamatórios/química , Integrina alfa3/metabolismo , Nanopartículas de Magnetita/química , Nanocompostos/química , Osteoblastos/metabolismo , Osteoclastos/metabolismo , Osteogênese/efeitos dos fármacos , Animais , Anti-Inflamatórios/farmacologia , Apoptose/efeitos dos fármacos , Biomarcadores/metabolismo , Diferenciação Celular/efeitos dos fármacos , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Microambiente Celular/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Integrina alfa3/genética , Campos Magnéticos , Camundongos , Osteoblastos/citologia , Transdução de Sinais , Relação Estrutura-Atividade , Propriedades de SuperfícieRESUMO
Lithium (Li+) ion due to its excellent bioactivity is one of the most well-studied element in bone-tissue engineering. In this study, we fabricated nanohydroxyapatite (nHAp) doped with Li+ ions (5â¯mol% Li+:nHAp) and co-doped with lanthanide ions. We investigated the effects of nHAp, 5â¯mol% Li+:nHAp or Li+ alone, on osteogenic differentiation of human Adipose Tissue-derived Stem Cells (hASCs), their proliferation, mitochondrial dynamics and apoptosis. Moreover, we monitored cell proliferation after treatment with samarium (III) (Sm3+) and europium (III) (Eu3+) ions co-doped 5â¯mol% Li+:nHAp as well as their luminescent property. The hASCs treated with 5â¯mol% Li+:nHAp and Li+ ions proliferated more rapidly and differentiated effectively than control cells without undergoing apoptosis. Both, 5â¯mol% Li+:nHAp and Li+ ions improved osteogenic differentiation of hASCs. Moreover they decreased expression of glycogen synthase kinase 3ß (GSK3ß) while increased ß-catenin mRNA level. In addition, Li+, nHAp and 5â¯mol% Li+:nHAp improved mitochondrial dynamics and enhanced expression of neural differentiation marker genes. Collectively, the study indicates on pro-osteogenic and anti-apoptotic properties of nHAp doped with Li+ and Li+ alone. Moreover, unique properties of 5â¯mol% Li+:nHAp and 5â¯mol% Li+:nHAp co-doped with rare earth ions, such as Sm3+ and Eu3+ have shed a promising light on their potential application in theranostics.
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Durapatita/química , Európio/farmacologia , Lítio/farmacologia , Células-Tronco Mesenquimais/metabolismo , Nanopartículas/química , Osteogênese/efeitos dos fármacos , Samário/farmacologia , Nanomedicina Teranóstica , Apoptose , Biomarcadores/metabolismo , Calcificação Fisiológica/efeitos dos fármacos , Cálcio/metabolismo , Diferenciação Celular/efeitos dos fármacos , Proliferação de Células , Sobrevivência Celular/efeitos dos fármacos , Citoesqueleto/efeitos dos fármacos , Citoesqueleto/metabolismo , Humanos , Íons , Leptina/genética , Leptina/metabolismo , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/efeitos dos fármacos , MicroRNAs/genética , MicroRNAs/metabolismo , Dinâmica Mitocondrial/efeitos dos fármacos , Nanopartículas/ultraestrutura , Nestina/genética , Nestina/metabolismo , Proteínas de Neurofilamentos/genética , Proteínas de Neurofilamentos/metabolismo , Osteogênese/genética , Osteopontina/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Espectroscopia de Infravermelho com Transformada de Fourier , Difração de Raios XRESUMO
Osteoconductive drug delivery system composed of nanocrystalline calcium phosphates (Ca10(PO4)6(OH)2/ß-Ca3(PO4)2) co-doped with Yb(3+)/Er(3+) ions loaded with Tetracycline antibiotic (TC) was developed. Their effect on human adipose derived mesenchymal stromal stem cells (hASCs) as a potential reconstructive biomaterial for bone tissue regeneration was studied. The XRD and TEM measurements were used in order to determine the crystal structure and morphology of the final products. The characteristics of nanocomposites with the TC and hASCs as potential regenerative materials as well as the antimicrobial activity of the nanoparticles against: Staphylococcus aureus ATCC 25923 as a model of the Gram-positive bacteria, Escherichia coli ATCC 8739 of the Gram-negative bacteria, were shown. These combinations can be a promising material for theranostic due to its regenerative, antimicrobial and fluorescent properties.