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1.
J Orthop Translat ; 38: 23-31, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36313979

RESUMO

Background: Geniposidic acid (GPA), one of the active components of Eucommia ulmoides, promote bone formation and treat osteoporosis by activating farnesoid X receptor (FXR). However, GPA has low oral availability and lack of bone targeting in the treatment of bone related diseases. With the development of modern technology, small molecules, amino acids, or aptamers are used for biological modification of drugs and target cells in bone tissue, which has become the trend of bone targeted research. Methods: In this study, SDSSD (an osteoblast-targeting peptide) were modified in GPA using Fmoc solid-phase synthesis technique to form a new SDSSD-GPA conjugate (SGPA). The bone targeting of SGPA was evaluated using in vivo imaging and cell co-culture. In vitro, the effect of SGPA on cytotoxicity, osteoblastic activity, and mineralization ability were studied in mouse primary osteoblasts (OBs). In vivo, the therapeutic effect of SGPA on osteoporosis using an ovariectomized (OVX) mouse model. The bone mass, histomorphometry, serum biochemical parameters, and the molecular mechanism were evaluated. Results: SGPA was enriched in OBs and tends to accumulate in bone tissue. In vitro, SGPA significantly enhanced the osteogenic activity and mineralization of OBs compared with GPA. In vivo, SGPA enhanced serum BALP and P1NP levels, increased the trabecular bone mass of the mice, and SGPA administration have a higher bone mineralization deposition rate than the GPA-treated mice. Moreover, SGPA significantly activated FXR and Runt-related transcription factor 2 (RUNX2). Conclusions: Collectively, SGPA is enriched into OBs, and promotes bone formation by activating FXR-RUNX2 signalling, effectively treating osteoporosis at relatively low doses. The translational potential of this article: This study demonstrates a more efficient and safe application of GPA in treating osteoporosis, provide a new concept for the bone targeted application of natural compounds.

2.
Bone Joint Res ; 11(12): 843-853, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36453022

RESUMO

AIMS: This study aimed to explore the role of small colony variants (SCVs) of Staphylococcus aureus in intraosseous invasion and colonization in patients with periprosthetic joint infection (PJI). METHODS: A PJI diagnosis was made according to the MusculoSkeletal Infection Society (MSIS) for PJI. Bone and tissue samples were collected intraoperatively and the intracellular invasion and intraosseous colonization were detected. Transcriptomics of PJI samples were analyzed and verified by polymerase chain reaction (PCR). RESULTS: SCVs can be isolated from samples collected from chronic PJIs intraoperatively. Transmission electron microscopy (TEM) and immunofluorescence (IF) showed that there was more S. aureus in bone samples collected from chronic PJIs, but much less in bone samples from acute PJIs, providing a potential mechanism of PJI. Immunofluorescence results showed that SCVs of S. aureus were more likely to invade osteoblasts in vitro. Furthermore, TEM and IF also demonstrated that SCVs of S. aureus were more likely to invade and colonize in vivo. Cluster analysis and principal component analysis (PCA) showed that there were substantial differences in gene expression profiles between chronic and acute PJI. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that these differentially expressed genes were enriched to chemokine-related signal pathways. PCR also verified these results. CONCLUSION: Our study has shown that the S. aureus SCVs have a greater ability to invade and colonize in bone, resulting in S. aureus remaining in bone tissues long-term, thus explaining the pathogenesis of chronic PJI.Cite this article: Bone Joint Res 2022;11(12):843-853.

3.
Front Endocrinol (Lausanne) ; 13: 1054827, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36452326

RESUMO

Long non-coding RNAs (lncRNAs) have been comprehensively implicated in various cellular functions by mediating transcriptional or post-transcriptional activities. MALAT1 is involved in the differentiation, proliferation, and apoptosis of multiple cell lines, including BMSCs, osteoblasts, osteoclasts, and chondrocytes. Interestingly, MALAT1 may interact with RNAs or proteins, regulating cellular processes. Recently, MALAT1 has been reported to be associated with the development of bone and cartilage diseases by orchestrating the signaling network. The involvement of MALAT1 in the pathological development of bone and cartilage diseases makes it available to be a potential biomarker for clinical diagnosis or prognosis. Although the potential mechanisms of MALAT1 in mediating the cellular processes of bone and cartilage diseases are still needed for further elucidation, MALAT1 shows great promise for drug development.


Assuntos
Doenças das Cartilagens , RNA Longo não Codificante , Humanos , RNA Longo não Codificante/genética , Doenças das Cartilagens/genética , Osteoclastos , Osteoblastos , Condrócitos
4.
Arch Med Sci ; 18(6): 1542-1557, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36457973

RESUMO

Introduction: Osteoblasts and osteoclasts are cells of osteoblastic origin, and are vital in homeostasis of the skeleton. miRs are important for functioning, survival and differentiation of osteoclasts. It has been reported previously that miR-23b-3p is involved in osteoporosis and in regulation of differentiation of osteoblasts. It is also involved in the process of bone formation. However, the role of miR-23b-3p in differentiation of osteoclasts remains unexplored. Material and methods: CSF-1 and ODF induced osteoclasts were used for the study. RNA isolation was done from TIB-71 cells. TRAP staining was done for TRAP-positive osteoclast formation. PIT assay for bone resorption was performed. For in vivo studies osteoclast-specific miR-23b-3p transgenic mice were developed. Results: The levels of miR-23b-3p were upregulated in bone marrow monocytes during osteoclastogenesis with colony stimulating factor-1 and osteoclast differentiation factor induction, which suggests that miR-23b-3p plays a crucial role in differentiation of osteoclasts. Over-expression of miR-23b-3p in bone marrow monocytes leads to osteoclastogenesis, whereas the inhibition ameliorates it. We further studied the function of miR-23b-3p via PI3K/AKT targeting the PTEN pathway. In vivo, osteoclast-specific miR-23b-3p transgenic mice showed suppressed PTEN and elevated osteoclast activity, and the mice showed decreased bone mineral density. Conclusions: The results suggest that miR-23b-3p regulates the differentiation of osteoclasts by targeting PTEN through the PI3K/AKT cascade.

5.
Artigo em Inglês | MEDLINE | ID: mdl-36462638

RESUMO

Static magnetic fields (SMFs), magnetic fields with constant intensity and orientation, have been extensively studied in the field of bone biology both fundamentally and clinically as a non-invasive physical factor. A large number of animal experiments and clinical studies have shown that SMFs have effective therapeutic effects on bone-related diseases such as non-healing fractures, bone non-union of bone implants, osteoporosis and osteoarthritis. The maintenance of bone health in adults depends on the basic functions of bone cells, such as bone formation by osteoblasts and bone resorption by osteoclasts. Numerous studies have revealed that SMFs can regulate the proliferation, differentiation, and function of bone tissue cells, including bone marrow mesenchymal stem cells (BMSCs), osteoblasts, bone marrow monocytes (BMMs), osteoclasts, and osteocytes. In this paper, the effects of SMFs on bone-related diseases and bone tissue cells are reviewed from both in vivo studies and in vitro studies, and the possible mechanisms are analyzed. In addition, some challenges that need to be further addressed in the research of SMF and bone are also discussed.

6.
Matrix Biol Plus ; 16: 100125, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36452176

RESUMO

Tumour development and progression is dependent upon tumour cell interaction with the tissue stroma. Bioengineering the tumour-stroma microenvironment (TME) into 3D biomimetic models is crucial to gain insight into tumour cell development and progression pathways and identify therapeutic targets. Ameloblastoma is a benign but locally aggressive epithelial odontogenic neoplasm that mainly occurs in the jawbone and can cause significant morbidity and sometimes death. The molecular mechanisms for ameloblastoma progression are poorly understood. A spatial model recapitulating the tumour and stroma was engineered to show that without a relevant stromal population, tumour invasion is quantitatively decreased. Where a relevant stroma was engineered in dense collagen populated by gingival fibroblasts, enhanced receptor activator of nuclear factor kappa-B ligand (RANKL) expression was observed and histopathological properties, including ameloblastoma tumour islands, developed and were quantified. Using human osteoblasts (bone stroma) further enhanced the biomimicry of ameloblastoma histopathological phenotypes. This work demonstrates the importance of the two key stromal populations, osteoblasts, and gingival fibroblasts, for accurate 3D biomimetic ameloblastoma modelling.

8.
Int J Biol Macromol ; 2022 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-36427609

RESUMO

Parathyroid hormone (PTH) regulates the expression of bone remodeling genes by enhancing the activity of Runx2 in osteoblasts. p300, a histone acetyltransferase, acetylated Runx2 to activate the expression of its target genes. PTH stimulated the expression of p300 in rat osteoblastic cells. Increasing studies suggested the potential of non-coding RNAs (ncRNAs), such as microRNAs (miRNAs) and circular RNAs (circRNAs), in regulating gene expression under both physiological and pathological conditions. In this study, we hypothesized that PTH regulates Runx2 activity via ncRNAs-mediated p300 expression in rat osteoblastic cells. Bioinformatics and experimental approaches identified PTH-upregulation of miR-130b-5p and circ_CUX1 that putatively target p300 and miR-130b-5p, respectively. An antisense-mediated knockdown of circ_CUX1 was performed to determine the sponging activity of circ_CUX1. Knockdown of circ_CUX1 promoted miR-130b-5p activity and reduced p300 expression, resulting in decreased Runx2 acetylation in rat osteoblastic cells. Further, bioinformatics analysis identified the possible signaling pathways that regulate Runx2 activity and osteoblast differentiation via circ_CUX1/miR-130b-5p/p300 axis. The predicted circ_CUX1/miR-130b-5p/p300 axis might pave the way for better diagnostic and therapeutic approaches for bone-related diseases.

9.
J Clin Biochem Nutr ; 71(3): 191-197, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36447486

RESUMO

Nitric oxide and reactive oxygen species regulate bone remodeling, which occurs via bone formation and resorption by osteoblasts and osteoclasts, respectively. Recently, we found that 8-nitro-cGMP, a second messenger of nitric oxide and reactive oxygen species, promotes osteoclastogenesis. Here, we investigated the formation and function of 8-nitro-cGMP in osteoblasts. Mouse calvarial osteoblasts were found to produce 8-nitro-cGMP, which was augmented by tumor necrosis factor-α (10 ng/ml) and interleukin-1ß (1 ng/ml). These cytokines suppressed osteoblastic differentiation in a NO synthase activity-dependent manner. Exogenous 8-nitro-cGMP (30 µmol/L) suppressed expression of osteoblastic phenotypes, including mineralization, in clear contrast to the enhancement of mineralization by osteoblasts induced by 8-bromo-cGMP, a cell membrane-permeable analog of cGMP. It is known that reactive sulfur species denitrates and degrades 8-nitro-cGMP. Mitochondrial cysteinyl-tRNA synthetase plays a crucial role in the endogenous production of RSS. The expression of osteoblastic phenotypes was suppressed by not only exogenous 8-nitro-cGMP but also by silencing of the Cars2 gene, indicating a role of endogenous 8-nitro-cGMP in suppressing the expression of osteoblastic phenotypes. These results suggest that 8-nitro-cGMP is a negative regulator of osteoblastic differentiation.

10.
Biochimie ; 2022 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-36336107

RESUMO

Osteoblasts are essential for bone formation and can perceive external mechanical stimuli, which are translated into biochemical responses that ultimately alter cell phenotypes and respond to environmental stimuli, described as mechanical transduction. These cells actively participate in osteogenesis and the formation and mineralisation of the extracellular bone matrix. This review summarises the basic physiological and biological mechanisms of five different physical stimuli, i.e. light, electricity, magnetism, force and sound, to induce osteogenesis; further, it summarises the effects of changing culture conditions on the morphology, structure and function of osteoblasts. These findings may provide a theoretical basis for further studies on bone physiology and pathology at the cytological level and will be useful in the clinical application of bone formation and bone regeneration technology.

11.
Int J Mol Sci ; 23(21)2022 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-36362346

RESUMO

Suffruticosol B (Suf-B) is a stilbene found in Paeonia suffruticosa ANDR., which has been traditionally used in medicine. Stilbenes and their derivatives possess various pharmacological effects, such as anticancer, anti-inflammatory, and anti-osteoporotic activities. This study aimed to explore the bone-forming activities and mechanisms of Suf-B in pre-osteoblasts. Herein, >99.9% pure Suf-B was isolated from P. suffruticosa methanolic extracts. High concentrations of Suf-B were cytotoxic, whereas low concentrations did not affect cytotoxicity in pre-osteoblasts. Under zero levels of cytotoxicity, Suf-B exhibited bone-forming abilities by enhancing alkaline phosphatase enzyme activities, bone matrix calcification, and expression levels with non-collagenous proteins. Suf-B induces intracellular signal transduction, leading to nuclear RUNX2 expression. Suf-B-stimulated differentiation showed increases in autophagy proteins and autophagosomes, as well as enhancement of osteoblast adhesion and transmigration on the ECM. These results indicate that Suf-B has osteogenic qualities related to differentiation, autophagy, adhesion, and migration. This also suggests that Suf-B could have a therapeutic effect as a phytomedicine in skeletal disorders.


Assuntos
Paeonia , Estilbenos , Osteogênese , Subunidade alfa 1 de Fator de Ligação ao Core/genética , Subunidade alfa 1 de Fator de Ligação ao Core/metabolismo , Osteoblastos/metabolismo , Autofagia , Paeonia/metabolismo , Estilbenos/farmacologia , Diferenciação Celular
12.
Materials (Basel) ; 15(21)2022 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-36363140

RESUMO

The current study aimed to assess the topographical and physical properties of a minimally invasive implant (MagiCore®: MC®, InnosBioSurg, IBS) and to evaluate its biological behavior compared to a gold standard implant (NobelParallel™: NB™, Nobel Biocare™). After surface characterization, the biological behavior assessment was conducted regarding human gingival fibroblasts (hGF) and osteoblast-like cells (MG63). Roughness values for NBTM were Ra = 1.28 µm and for MC® they were Ra = 2.02 µm. Alamar BlueTM assay LIVE/DEADTM staining results indicated equivalent biological development regarding both cell types for the two implants. Significant enhancement was found for hGF ALP activity in the presence of the two tested implants in a time-dependent manner from day 7 to day 14 (** p < 0.01). Alizarin red staining demonstrated significant calcium deposition enhancement when cells were interfaced with the NB™ compared to the MC® implant (** p < 0.05). Moreover, SEM and confocal imaging revealed good cell adhesion with a denser cellular layer on the MC® than the NB™ surface. The MC® cytocompatibility was ranked as equivalent to the gold standard implant despite the surface properties differences. These findings provide new insights about the minimally invasive implant's biological behavior and its potential clinical implication in different implantology situations.

13.
Cells ; 11(21)2022 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-36359752

RESUMO

The culture of osteoblasts (OB) of human origin is a useful experimental model in studying bone biology, osteogenic differentiation, functions of bone proteins, oncological processes in bone tissue, testing drugs against bone desires, and many other fields. The purpose of the present study is to share a workflow that has established the conditions to efficiently isolate and grow OB cells obtained from surgically removed bones from human donors. The protocol described here also shows how to determine cell phenotype. Here we provide characteristics of cells isolated by this protocol that might help researchers to decide if such OB are suitable for the purposes of their study. Osteoblasts isolated from collagenase-treated explants of adult bones are able to proliferate and keep their phenotype in culture. OB cells have high synthetic properties. They express osteomarkers, such as RUNX2, osteocalcin, BMP2, and osteopontin both in control conditions and in an osteogenic medium that could be estimated by qPCR and immunocytochemical staining and by Western blotting. Induction of osteogenic differentiation does not dramatically influence the synthetic properties of OB cells, while the cells gain the ability to extracellular mineralization only in an osteogenic medium.


Assuntos
Osteoblastos , Osteogênese , Humanos , Osteogênese/genética , Osteoblastos/metabolismo , Diferenciação Celular , Osteocalcina/metabolismo , Osso e Ossos/metabolismo
14.
J Tissue Eng Regen Med ; 16(12): 1184-1195, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36348261

RESUMO

Blood vessel formation is the prerequisite for the survival and growth of tissue-engineered bone. Mineralized osteoblasts (MOBs) have been shown to regulate angiogenesis through the secretion of exosomes containing various pro-angiogenic factors. However, whether the mineralized osteoblast-derived exosomes (MOB-Exos) containing let-7f-5p can regulate the angiogenesis of endothelial cells (ECs) is still unknown. In this study, the angiogenic capabilities of ECs respectively treated with MOB-Exos, let-7f-5p mimicked MOB-Exos (miR mimic group), and let-7f-5p inhibited MOB-Exos (miR inhibitor group) were compared through in vitro and in vivo studies. Moreover, the potential mechanism of MOB-Exo let-7f-5p regulating angiogenesis was explored by verifying the role of the Erk1/2 signaling pathway and target gene DUSP1. The results showed that MOB-Exos could significantly promote the angiogenesis of ECs, which could be enhanced by mimicked exosomal let-7f-5p and attenuated by inhibited exosomal let-7f-5p. Let-7f-5p could suppress the luciferase activity of wide-type DUSP1, and the mutation of DUSP1 could abrogate the repressive ability of let-7f-5p. Furthermore, the expression of DUSP1 exhibited a reversed trend to that of pErk1/2. The expression of pErk1/2 was significantly higher in the miR mimic group and lower in the miR inhibitor group than that in the MOB-Exos group, while inhibition of pErk1/2 could partly impair the angiogenic capabilities of ECs. In conclusion, we concluded that exosomal let-7f-5p derived from MOBs could promote the angiogenesis of ECs via activating the DUSP1/Erk1/2 signaling pathway, which might be a promising target for promoting the angiogenesis of tissue-engineered bone.


Assuntos
Exossomos , MicroRNAs , Fosfatase 1 de Especificidade Dupla/metabolismo , Células Endoteliais/metabolismo , Exossomos/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Neovascularização Patológica , Osteoblastos/metabolismo , Transdução de Sinais , Animais
15.
Front Physiol ; 13: 1052429, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36439254

RESUMO

Osteoporosis is a common endocrinologic disorder characterized as a chronic bone loss condition. Sexual dimorphism is ubiquitous in the incidence of osteoporosis with post-menopausal women being acutely affected. Gonadal sex hormones including estrogen act as crucial regulators of bone mass; therefore, loss of such hormones leads to an imbalance in skeletal turnover leading to osteoporosis. Estrogen can influence both bone formation as well as resorption by reducing osteoblast activity and enhancing osteoclastogenesis. Additionally, estrogen is a potent regulator of systemic metabolism. Recent studies have provided clues that estrogenic effect on bone might also involve alterations in bone cell metabolism and bioenergetic potential. While direct effects of gonadal hormones ability to alter intracellular metabolism of bone cells has not been studied, there is precedence within the literature that this is occurring and contributing to post-menopausal bone loss. This review aims to serve as a perspective piece detailing the prospective role of gonadal hormones regulating bone cell metabolic potential.

16.
Free Radic Biol Med ; 193(Pt 2): 595-609, 2022 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-36372285

RESUMO

NADPH oxidase 4 (Nox4) is the main source of reactive oxygen species, which promote osteoclast formation and lead to bone loss, thereby causing osteoporosis. However, the role of Nox4 in osteoblasts during early development remains unclear. We used zebrafish to study the effect of Nox4 deletion on bone mineralization in early development. nox4-/- zebrafish showed decreased bone mineralization during early development and significantly reduced numbers of osteoblasts, osteoclasts, and chondrocytes. Transcriptome sequencing showed that the TGF-ß signaling pathway was significantly disrupted in nox4-/- zebrafish. Inhibiting TGF-ß signaling rescued the abnormal bone development caused by nox4 deletion and increased the number of osteoblasts. We used Saos-2 human osteosarcoma cells to confirm our results, which clarified the role of Nox4 in human osteoblasts. Our results demonstrate the mechanism of reduced bone mineralization in early development and provide a basis for the clinical treatment of osteoporosis.


Assuntos
Osteoporose , Fator de Crescimento Transformador beta , Animais , Humanos , NADPH Oxidase 4/genética , NADPH Oxidase 4/metabolismo , Fator de Crescimento Transformador beta/metabolismo , Peixe-Zebra/genética , Peixe-Zebra/metabolismo , Osteoblastos/metabolismo , Transdução de Sinais , Osteoporose/metabolismo
17.
J Orthop Sci ; 2022 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-36371341

RESUMO

BACKGROUND: Intrawound vancomycin powder is effective in preventing surgical site infection after spine surgery. In a previous study, vancomycin-induced cytotoxicity in osteoblasts was investigated in vitro, and vitamin D3 was verified to be a candidate drug aiding recovery from vancomycin-induced cytotoxicity. The treatment practices involving osteogenesis-promoting drugs vary widely. Teriparatide, an anabolic agent, highly promotes bone formation by inducing osteoblast activation, increasing bone formation and mineral density, and preventing vertebral fractures. Hence, teriparatide may be administered in combination with vancomycin. METHODS: MC3T3-E1 cells were cultured in minimum essential medium supplemented with 10% fetal bovine serum at 37 °C in a humidified incubator containing 5% CO2. The experimental concentrations of vancomycin (2500, 5000, and 7500 µg/mL) were determined based on previous reports and our preliminary experiments. Teriparatide (100 ng/mL) was administered concomitantly to prevent cytotoxicity in osteoblasts, using pulsed vancomycin for 24 h (measured at 1, 3, and 7 days). Cell numbers and morphological changes in cells treated with vancomycin or vancomycin plus 100 ng/mL teriparatide were measured. Osteoblast differentiation was assessed using alkaline phosphatase staining, alkaline phosphatase activity, and alizarin red S staining. RESULTS: Teriparatide showed a recovery effect when vancomycin (7500 µg/mL) was administered only for 24 h. Microscopic examination revealed that teriparatide had a protective effect on osteoblasts exposed to 7500 µg/mL vancomycin. Addition of teriparatide led to the recovery of alkaline phosphatase staining and alizarin red staining. CONCLUSION: Vancomycin-induced cytotoxicity in osteoblasts could be inhibited by administering teriparatide concomitantly with vancomycin.

18.
Br J Haematol ; 2022 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-36354085

RESUMO

While the bone marrow (BM) microenvironment is significantly remodelled in acute myeloid leukaemia (AML), molecular insight into AML-specific alterations in the microenvironment has been historically limited by the analysis of liquid marrow aspirates rather than core biopsies that contain solid-phase BM stroma. We assessed the effect of anthracycline- and cytarabine-based induction chemotherapy on both haematopoietic and non-haematopoietic cells directly in core BM biopsies using RNA-seq and histological analysis. We compared matched human core BM biopsies at diagnosis and 2 weeks after cytarabine- and anthracycline-based induction therapy in responders (<5% blasts present after treatment) and non-responders (≥5% blasts present after treatment). Our data indicated enrichment in vimentin (VIM), platelet-derived growth factor receptor beta (PDGFRB) and Snail family transcriptional repressor 2 (SNAI2) transcripts in responders, consistent with the reactivation of the mesenchymal population in the BM stroma. Enrichment of osteoblast maturation-related transcripts of biglycan (BGN), osteopontin (SPP1) and osteonectin (SPARC) was observed in non-responders. To the best of our knowledge, this is the first report demonstrating distinct osteogenic and mesenchymal transcriptome profiles specific to AML response to induction chemotherapy assessed directly in core BM biopsies. Detailing treatment response-specific alterations in the BM stroma may inform optimised therapeutic strategies for AML.

19.
Front Endocrinol (Lausanne) ; 13: 1032614, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36339402

RESUMO

Multiple causes may contribute to osteoporosis, characterized by a loss in bone mass and density as a consequence of the degradation of bone microstructure and a resultant rise in bone fragility. Recently, increasing attention has been paid to the role of necroptosis in the development of osteoporosis. Necroptosis is orchestrated by a set of proteins known as receptor-interacting protein kinase (RIPK)1, RIPK3, and mixed lineage kinase domain-like protein (MLKL). A necrosome is formed by MLKL, RIPK1, RIPK3, and RIPK3-RIPK3. A dissociated MLKL forms pores in the plasma membrane and eventually leads to necroptosis after translocating from the necrosome. In this review, we discuss a detailed understanding of necroptosis and its associated processes, a better understanding of its interactions with osteoclasts, osteoblasts, and osteocytes, and the associations between necroptosis and diabetic osteoporosis, steroid-induced osteoporosis, and postmenopausal osteoporosis. In addition, a variety of experimental medicines capable of modulating crucial necroptosis processes are highlighted. It's important to note that this is the first review paper to consolidate current data on the role of necroptosis in osteoporosis, and it offers fresh hope for the future treatment of this disease.


Assuntos
Necroptose , Osteoporose , Humanos , Proteínas Quinases , Osteoporose/etiologia , Osteoporose/prevenção & controle
20.
Polymers (Basel) ; 14(22)2022 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-36433040

RESUMO

Grafting polyethylene glycol (PEG) onto a polymer's surface is widely used to improve biocompatibility by reducing protein and cell adhesion. Although PEG is considered to be bioinert, its incorporation onto biomaterials has shown to improve cell viability depending on the amount and molecular weight (MW) used. This phenomenon was studied here by grafting PEG of three MW onto polyurethane (PU) substrata at three molar concentrations to assess their effect on PU surface properties and on the viability of osteoblasts and fibroblasts. PEG formed a covering on the substrata which increased the hydrophilicity and surface energy of PUs. Among the results, it was observed that osteoblast viability increased for all MW and grafting densities of PEG employed compared with unmodified PU. However, fibroblast viability only increased at certain combinations of MW and grafting densities of PEG, suggesting an optimal level of these parameters. PEG grafting also promoted a more spread cell morphology than that exhibited by unmodified PU; nevertheless, cells became apoptotic-like as PEG MW and grafting density were increased. These effects on cells could be due to PEG affecting culture medium pH, which became more alkaline at higher MW and concentrations of PEG. Results support the hypothesis that surface energy of PU substrates can be tuned by controlling the MW and grafting density of PEG, but these parameters should be optimized to promote cell viability without inducing apoptotic-like behavior.

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