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1.
J Dent ; 143: 104899, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38428719

RESUMO

OBJECTIVES: Demineralized bone matrix (DBM) is a well-established bone graft material widely accepted by dentists and the public for its favorable osteoconductivity and osteoinductive potential. This article aimed to provide a narrative review of the current therapeutic applications and limitations of DBM in maxillofacial bone defects. STUDY SELECTION, DATA, AND SOURCES: Randomized controlled trials, prospective or retrospective clinical studies, case series and reports, and systematic reviews. MEDLINE, PubMed, and Google Scholar were searched using keywords. CONCLUSIONS: Some evidence supported the therapeutic application of DBM in periodontal intrabony defects, maxillary sinus lifts, ridge preservation, ridge augmentation, alveolar cleft repair, orthognathic surgery, and other regional maxillofacial bone defects. However, the limitations of DBM should be considered when using it, including potential low immunogenicity, instability of osteoinductive potential, handling of the graft material, and patient acceptance. CLINICAL SIGNIFICANCE: With the increasing demand for the treatment of maxillofacial bone defects, DBM is likely to play a greater role as a promising bone graft material. Safe and effective combination treatment strategies and how to maintain a stable osteoinductive potential will be the future challenges of DBM research.


Assuntos
Matriz Óssea , Regeneração Óssea , Humanos , Matriz Óssea/transplante , Estudos Prospectivos , Estudos Retrospectivos , Resultado do Tratamento , Transplante Ósseo
2.
Int J Oral Maxillofac Implants ; 39(1): 79-86, 2024 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-38416002

RESUMO

PURPOSE: To evaluate the influence of initial implant protrusion within the subantral space on hard tissue gain for implants placed simultaneously with transcrestal sinus floor elevation (TSFE) with a biomaterial. MATERIALS AND METHODS: A total of 50 implants were placed after TSFE in 44 patients using either a human demineralized bone matrix or a deproteinized bone mineral matrix. Intraoral radiographs were obtained before and immediately after surgery. CBCT scans were obtained at the last follow-up (mean: 6.6 years). RESULTS: The initial bone crest height was 4.6 ± 1.4 mm, and the initial protrusion of the implants above the sinus floor was 3.5 ± 1.4 mm. At the follow-up assessments, the hard tissue mean gain was 2.5 ± 1.5 mm, resulting in a mean residual protrusion of 1.1 ± 1.3 mm. Only 10 implants did not protrude above the apical level of hard tissue. Positive correlations were found between hard tissue gain and initial protrusion (r = 0.55; 95% CI: 0.32 to 0.72; P = .0001), between the initial and final protrusions (r = 0.38; 95% CI: 0.10 to 0.60; P = .007), and between the follow-up period and final protrusion (r = 0.35; 95% CI: 0.07 to 0.58; P = .012). CONCLUSIONS: The higher the initial protrusion was, the higher were the hard tissue gain and the final protrusion of the implant above the apical level of the hard tissue.


Assuntos
Osteogênese , Levantamento do Assoalho do Seio Maxilar , Humanos , Materiais Biocompatíveis , Matriz Óssea
3.
J Food Sci ; 89(3): 1540-1553, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38343300

RESUMO

Bovine bone is an animal-origin matrix rich in type I collagen (COL I) and it necessitates prior demineralization and makes COL I available. This study investigated the ossein-hydroxyapatite physicochemical properties evaluation as a result of processing and solubilization by acids and revealed the bone matrix demineralization and making COL I available. The tibia residue from bovine sources was processed, ground, and transformed into bone matrix powder. The bone matrix was solubilized in acetic acid followed by lactic acid. The bone matrix was evaluated as a result of processing and solubilization by acids: ossein and hydroxyapatite percentages by nitrogen and ash content, mineral content, particle size distribution, Fourier-transformation infrared spectroscopy, x-ray diffraction, and scanning electron microscope. For the obtained residual extracts, pH and mineral content were evaluated. The solubilization by acids affected the ossein-hydroxyapatite physicochemical properties, and the bone matrix solubilized by acetic and lactic acid showed the preservation of the ossein alongside the loss of hydroxyapatite. The processing and the solubilization by acids were revealed to be a  alternative to bone matrix demineralization and enabling the accessibility of bone COL I. PRACTICAL APPLICATION: Bovine bone is an abundant type I collagen source, but processing maneuvers and demineralization effect present limitations due to the rigidity of the structural components. Exploring methodologies to process and demineralize will allow type I collagen to be obtained from the bone source, and direct and amplify the potentialities in the chemical and food industries. The research focused on bone sources and collagen availability holds paramount significance, and promotes repurposing agribusiness residues and development of protein-base products.


Assuntos
Colágeno Tipo I , Durapatita , Animais , Bovinos , Matriz Óssea , Colágeno/química , Ácido Láctico
4.
Tissue Cell ; 87: 102329, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38367326

RESUMO

High-temperature requirement A1 (HtrA1), a multidomain serine protease acting on Extracellular matrix (ECM) rearrangement, is also secreted by osteoblasts and osteoclasts. Recent and conflicting literature highlights HtrA1's role as a controller of bone remodeling, proposing it as a possible target for pathologies with unbalanced bone resorption, like Osteoporosis (OP). To add knowledge on this molecule function in bone physiopathology, here we compared HtrA1 distribution in the ECM of healthy (H) and OP bone tissue, also examining its localization in the sites of new bone formation. HtrA1 was homogeneously expressed in the mature bone ECM of H tissue showing a 55.6 ± 16.4% of the stained area, with a significant (p=0.0001) decrease in OP percentage stained area (21.1 ± 13.1). Moreover, HtrA1 was present in the endosteum and cells involved in osteogenesis, mainly in those "entrapped" in woven bone, whereas osteocytes in mature lamellar bone were negative. Based on our previous observation in OP tissue of a significantly increased expression of Decorin and Osteocalcin, both involved in bone mineralization and remodeling and equally substrates for HtrA1, we speculate that HtrA1 by controlling the proper amount of Decorin and Osteocalcin favors normal bone maturation and mineralization. Besides, we suggest that late-osteoblasts and pre-osteocytes secrete HtrA1 in the adjacent matrix whilst proceeding with their maturation and that HtrA1 expression is further modified during the remodeling from woven to the lamellar bone. Overall, our data suggest HtrA1 as a positive regulator of bone matrix formation and maturation: its reduced expression in mature OP bone, affecting protein content and distribution, could hamper correct bone remodeling and mineralization.


Assuntos
Osteoporose , Serina Proteases , Humanos , Osteocalcina/metabolismo , Serina Proteases/metabolismo , Matriz Óssea/metabolismo , Decorina/metabolismo , Serina Peptidase 1 de Requerimento de Alta Temperatura A/genética , Serina Peptidase 1 de Requerimento de Alta Temperatura A/metabolismo , Serina Endopeptidases/genética , Serina Endopeptidases/metabolismo , Osso e Ossos/metabolismo , Matriz Extracelular/metabolismo , Osteoporose/genética
5.
Medicina (Kaunas) ; 60(2)2024 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-38399552

RESUMO

Background and Objectives: Posterior lumbar interbody fusion (PLIF) plays a crucial role in addressing various spinal disorders. The success of PLIF is contingent upon achieving bone fusion, as failure can lead to adverse clinical outcomes. Demineralized bone matrix (DBM) has emerged as a promising solution for promoting fusion due to its unique combination of osteoinductive and osteoconductive properties. This study aims to compare the effectiveness of three distinct DBMs (Exfuse®, Bongener®, and Bonfuse®) in achieving fusion rates in PLIF surgery. Materials and Methods: A retrospective review was conducted on 236 consecutive patients undergoing PLIF between September 2016 and February 2019. Patients over 50 years old with degenerative lumbar disease, receiving DBM, and following up for more than 12 months after surgery were included. Fusion was evaluated using the Bridwell grading system. Bridwell grades 1 and 2 were defined as 'fusion', while grades 3 and 4 were considered 'non-fusion.' Clinical outcomes were assessed using visual analog scale (VAS) scores for pain, the Oswestry disability index (ODI), and the European quality of life-5 (EQ-5D). Results: Fusion rates were 88.3% for Exfuse, 94.3% for Bongener, and 87.7% for Bonfuse, with no significant differences. All groups exhibited significant improvement in clinical outcomes at 12 months after surgery, but no significant differences were observed among the three groups. Conclusions: There were no significant differences in fusion rates and clinical outcomes among Exfuse, Bongener, and Bonfuse in PLIF surgery.


Assuntos
Doenças da Coluna Vertebral , Fusão Vertebral , Humanos , Pessoa de Meia-Idade , Matriz Óssea , Qualidade de Vida , Vértebras Lombares/cirurgia , Estudos Retrospectivos , Resultado do Tratamento
6.
Int J Cancer ; 154(9): 1626-1638, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38196144

RESUMO

Due to the lack of a precise in vitro model that can mimic the nature microenvironment in osteosarcoma, the understanding of its resistance to chemical drugs remains limited. Here, we report a novel three-dimensional model of osteosarcoma constructed by seeding tumor cells (MG-63 and MNNG/HOS Cl no. 5) within demineralized bone matrix scaffolds. Demineralized bone matrix scaffolds retain the original components of the natural bone matrix (hydroxyapatite and collagen type I), and possess good biocompatibility allowing osteosarcoma cells to proliferate and aggregate into clusters within the pores. Growing within the scaffold conferred elevated resistance to doxorubicin on MG-63 and MNNG/HOS Cl no. 5 cell lines as compared to two-dimensional cultures. Transcriptomic analysis showed an increased enrichment for drug resistance genes along with enhanced glutamine metabolism in osteosarcoma cells in demineralized bone matrix scaffolds. Inhibition of glutamine metabolism resulted in a decrease in drug resistance of osteosarcoma, which could be restored by α-ketoglutarate supplementation. Overall, our study suggests that microenvironmental cues in demineralized bone matrix scaffolds can enhance osteosarcoma drug responses and that targeting glutamine metabolism may be a strategy for treating osteosarcoma drug resistance.


Assuntos
Neoplasias Ósseas , Osteossarcoma , Humanos , Glutamina , Matriz Óssea/metabolismo , Matriz Óssea/patologia , Metilnitronitrosoguanidina/uso terapêutico , Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/genética , Neoplasias Ósseas/metabolismo , Osteossarcoma/tratamento farmacológico , Osteossarcoma/genética , Osteossarcoma/metabolismo , Linhagem Celular Tumoral , Resistência a Medicamentos , Microambiente Tumoral
7.
J Biomed Mater Res B Appl Biomater ; 112(1): e35329, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37898921

RESUMO

We engineered an in vitro model of bioartificial 3D bone organoid consistent with an anatomical and vascular microenvironment common to mammalian flat and short bones. To achieve this, we chose the decellularized-decalcified matrix of the adult male rat scapula, implemented with the reconstruction of its intrinsic vessels, obtained through an original intravascular perfusion with polylevolactic (PLLA), followed by coating of the PLLA-fabricated vascularization with rat tail collagen. As a result, the 3D bone and vascular geometry of the native bone cortical and cancellous compartments was reproduced, and the rat tail collagen-PLLA biomaterial could in vitro act as a surrogate of the perivascular extracellular matrix (ECM) around the wall of the biomaterial-reconstituted cancellous vessels. As a proof-of-concept of cell compatibility and site-dependent osteoinductive properties of this bioartificial 3D construct, we show that it in vitro leads to a time-dependent microtopographic positioning of rat mesenchymal stromal cells (MSCs), initiating an osteogenic fate in relation to the bone compartment. In addition, coating of PLLA-reconstructed vessels with rat tail collagen favored perivascular attachment and survival of MSC-like cells (mouse embryonic fibroblasts), confirming its potentiality as a perivascular stroma for triggering competence of seeded MSCs. Finally, in vivo radiographic topography of bone lesions in the human jaw and foot tarsus of subjects with primary osteoporosis revealed selective bone cortical versus cancellous involvement, suggesting usefulness of a human 3D bone organoid engineered with the same principles of our rat organoid, to in vitro investigate compartment-dependent activities of human MSC in flat and short bones under experimental osteoporotic challenge. We conclude that our 3D bioartificial construct offers a reliable replica of flat and short bones microanatomy, and promises to help in building a compartment-dependent mechanistic perspective of bone remodeling, including the microtopographic dysregulation of osteoporosis.


Assuntos
Matriz Óssea , Osteoporose , Adulto , Masculino , Ratos , Animais , Humanos , Camundongos , Tecidos Suporte , Diferenciação Celular , Fibroblastos , Matriz Extracelular , Colágeno , Osteogênese , Organoides , Materiais Biocompatíveis , Células Cultivadas , Engenharia Tecidual , Mamíferos
8.
Clin Oral Implants Res ; 35(1): 114-130, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37966057

RESUMO

OBJECTIVES: To date, no clinical studies have investigated the effect of using resorbable collagen membrane in conjunction with customized titanium mesh to promote bone formation in guided bone regeneration. Therefore, a non-inferiority analysis (one-sided 95% CI approach) was designed to compare the augmented bone gained using meshes with and without collagen membranes, through histological and histomorphometric investigations. MATERIALS AND METHODS: Thirty patients undergoing bone augmentation procedures at both maxillary and mandible sites were randomly treated with customized titanium meshes alone (M-, n = 15) or covered with resorbable membrane (M+, n = 15), in both cases filled with autogenous bone and xenograft. After 6 months of healing, bone tissue biopsies were taken from the augmented region. The bone tissue (B.Ar), grafting material (G.Ar), and non-mineralized tissue (NMT.Ar) areas were quantified through histomorphometric analysis, as were the osteoid area (O.Ar) and its width. RESULTS: Collagen membrane did not appear to significantly influence the investigated parameters: B.Ar, G.Ar, NMT.Ar, and O.Ar were similar between Group M- (34.3%, 11.5%, 54.1%, 1.95 µm2 , respectively) and Group M+ (35.3%, 14.6%, 50.2%, and 1.75 µm2 , respectively). Considering the overall population, significantly higher rates of newly formed bone were obtained in mandibular sites, while non-mineralized and dense connective tissue rates were higher in the maxilla (p < .05). CONCLUSIONS: The application of collagen membrane over titanium mesh did not lead to significant results. Bone formation appeared significantly different in the maxilla compared with the mandible. Additional studies are required to further investigate the issues observed.


Assuntos
Aumento do Rebordo Alveolar , Implantes Dentários , Humanos , Titânio , Aumento do Rebordo Alveolar/métodos , Colágeno/uso terapêutico , Regeneração Óssea , Matriz Óssea , Transplante Ósseo/métodos , Membranas Artificiais , Telas Cirúrgicas
9.
Ann Anat ; 252: 152203, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38128745

RESUMO

BACKGROUND: Bone defects lead to dramatic changes in the quality of life. Acellular dermal matrix (ADM) and decellularized bone matrix (DBM) are natural scaffolds for tissue regeneration. The microcarrier scaffolds enable better vascularization and cell proliferation. This study compared the effect of microcarrier forms of DBM and ADM-loaded with adipose stem cells (ASCs) in the repair of compact bone defect in-vivo. METHODS: Fifty-four male rats were divided into 4 groups; (i) Group (Gp) I: sham control; (ii) GpII: underwent femur bone defect induction and left to heal spontaneously; (iii) GpIII (ADM-Gp): included 2 subgroups; IIIa and IIIb: the bone defects were filled with non-loaded ADM and ADM-loaded with ASCs, respectively; (iv) GpIV (DBM-Gp): included 2 subgroups; IVa and IVb: the bone defects were filled with non-loaded DBM and DBM-loaded with ASCs, respectively. Animals were euthanized after 1, 2 and 3 months and their femur sections were stained with H&E, Masson's trichrome and immunohistochemistry for CD31, osteopontin and osteocalcin. RESULTS: Histological analysis illustrated limited bone regeneration in the cortical defect of GpII after 3 months. The histomorphometric analysis showed significant delayed mature collagen deposition as well as CD31, osteopontin and osteocalcin expression. Superior capacity of new bone regeneration was detected with bio-scaffold micro-carriers; loaded or non-loaded with ASCs. However, DBM-loaded with ASCs displayed enhanced regeneration properties confirmed by the apparently normal architecture of the new bone and accelerated expression of CD31, osteopontin and osteocalcin in the regenerated bone after 3 months. CONCLUSIONS: We concluded that decellularized scaffolds significantly improved compact bone regeneration with superiority of ASCs seeded-bone scaffolds.


Assuntos
Derme Acelular , Osteopontina , Ratos , Masculino , Animais , Matriz Óssea , Osteocalcina , Qualidade de Vida , Regeneração Óssea , Células-Tronco , Tecidos Suporte/química , Osteogênese
10.
J Oral Biosci ; 66(1): 232-240, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38110178

RESUMO

OBJECTIVES: The prevention of implant-associated infections is becoming increasingly clinically important in the field of dentistry. Extensive investigations into the development of innovative antibacterial materials that interact effectively to reinforce their functionality are currently being conducted in the biomedical sector. In the present study, a novel dental nano putty (D-nP) has been developed using demineralized bone matrix (DBM), calcium sulfate hemihydrate (CSH), curcumin nanoparticles (CU-NPs), and silver nanoparticles (AgNPs). METHODS: The produced D-nP was evaluated using physicochemical, mechanical, and in vitro analyses. Surface characterization, particularly the analysis of calcium and phosphorus content, was performed before and after immersion in the simulated body fluid (SBF). In addition, the impact of surface treatment on biological activity was studied. RESULTS: The results showed that the mechanical properties of the D-nP were outstanding and its performance is promising. D-nP exhibited excellent antibacterial activity against Actinomyces naeslundii (5.22 ± 0.07 mm) and Streptococcus oralis (5.41 ± 0.1 mm). The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay was conducted using MG-63 osteoblast cells, which exhibited 95 % viability in D-nP. CONCLUSIONS: Based on these characterization results, the D-nP developed in this study exhibited excellent performance for tooth tissue in bone repair.


Assuntos
Curcumina , Implantes Dentários , Nanopartículas Metálicas , Apatitas , Prata/farmacologia , Prata/química , Curcumina/farmacologia , Nanopartículas Metálicas/uso terapêutico , Nanopartículas Metálicas/química , Matriz Óssea , Antibacterianos/farmacologia , Antibacterianos/química
11.
ACS Biomater Sci Eng ; 10(1): 515-524, 2024 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-38150512

RESUMO

Immunoregulatory and vascularized microenvironments play an important role in bone regeneration; however, the precise regulation for vascularization and inflammatory reactions remains elusive during bone repair. In this study, by means of subcutaneous preimplantation, we successfully constructed demineralized bone matrix (DBM) grafts with immunoregulatory and vascularized microenvironments. According to the current results, at the early time points (days 1 and 3), subcutaneously implanted DBM grafts recruited a large number of pro-inflammatory M1 macrophages with positive expression of CD68 and iNOS, while at the later time points (days 7 and 14), these inflammatory cells gradually subsided, accompanying increased presence of anti-inflammatory M2 macrophages with positive expression of CD206 and Arg-1, indicating a gradually enhanced anti-inflammatory microenvironment. At the same time, the gradually increased angiogenesis was observed in the DBM grafts with implantation time. In addition, the positive cells of CD105, CD73, and CD90 were observed in the inner region of the DBM grafts, implying the homing of mesenchymal stem cells. The repair results of cranial bone defects in a rat model further confirmed that the subcutaneous DBM xenografts at 7 days significantly improved bone regeneration. In summary, we developed a simple and novel strategy for bone regeneration mediated by anti-inflammatory microenvironment, prevascularization, and endogenous stem cell homing.


Assuntos
Matriz Óssea , Osteogênese , Humanos , Ratos , Animais , Xenoenxertos , Matriz Óssea/metabolismo , Matriz Óssea/transplante , Células-Tronco , Anti-Inflamatórios/metabolismo
12.
J Clin Periodontol ; 51(3): 338-353, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38110189

RESUMO

AIM: Recombinant bone matrix (RBM) is a newly conceived and engineered porous bone graft granule of average size 600 µm composed of purified recombinant collagen peptide. We sought to examine the behaviour with time of RBM that was grafted in the canine tooth extraction socket. MATERIALS AND METHODS: The canine tooth extraction socket of the hemisectioned mandibular third premolar distal root was grafted with RBM granules, whereas the opposite side extraction socket served as non-grafted control. The mandibular samples were harvested at 1, 3 and 6 months of healing and subjected to micro-CT imaging and decalcified paraffin-embedded histology. Separately, the effect of RBM was compared with that of deproteinized cancellous bovine bone (DCBB) and bovine atelocollagen plug (BACP) in the canine tooth extraction model at 3 months of healing. RESULTS: RBM maintained the grafted space in the socket and the gingival connective tissue until new bone was formed within its porous space. The regenerated bone was highly vascularized and continued to mature, while RBM was completely bioresorbed by 6 months. The buccal and lingual alveolar ridge heights of the RBM-grafted extraction socket was better preserved than those of non-grafted control sockets. The degree of socket preservation by RBM was equivalent to that by DCBB, although their healing mechanisms were different. CONCLUSIONS: This study demonstrated that RBM induced controlled active bone regeneration and preserved the extraction socket structure in a canine model. Bioresorbable RBM engineered without animal or human source materials presents a novel bone graft category with robust bone regenerative property.


Assuntos
Perda do Osso Alveolar , Aumento do Rebordo Alveolar , Substitutos Ósseos , Humanos , Animais , Bovinos , Matriz Óssea/transplante , Alvéolo Dental/cirurgia , Alvéolo Dental/patologia , Regeneração Óssea , Proteínas Recombinantes , Extração Dentária , Perda do Osso Alveolar/patologia , Aumento do Rebordo Alveolar/métodos
13.
Int J Oral Maxillofac Implants ; 38(6): 1175-1181, 2023 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-38085749

RESUMO

PURPOSE: To investigate bone regeneration among three different bone graft materials in a rat calvarum model. MATERIALS AND METHODS: A total of 24 rats had two 5-mm defects placed per calvarial. Rats were divided into four groups: bovine xenograft (XG), demineralized bone matrix (DBM), mineralized bone graft (MBG), and collagen membrane control (CC). Within each group, samples were collected at two time points: 4 weeks (T4) and 8 weeks (T8). Bone regeneration was assessed by microcomputed tomography (micro-CT) imaging and was analyzed using MATLAB software. Additionally, the fixed samples were subsequently demineralized for immunohistochemistry and histomorphometry. Slides were mounted and stained with hematoxylin and eosin (H&E) stain as well as bone morphogenetic protein 2 (BMP-2) and runt-related transcription factor 2 (RUNX2) markers. The numbers of positive cells/area were calculated for each group and analyzed. RESULTS: At 4 weeks, DBM showed low mineral density (7.7%) compared to the control (25.2%), but increased dramatically at 8 weeks (DBM, T8 = 27.6%; CC, T8 = 27.2%). Xenograft material showed an increase in mineral desnity between T4 and T8 (XG, T4 = 25.0%; XG, T8 = 32.3%). MBG remained consistent over the 8-week trial period (MBG, T4 = 30.4%; MBG, T8 = 30.4%). BMP-2 expression was present in cells adherent to all graft materials. RUNX2 expression was also observed in cells adherent to all graft materials, indicating that during the 4- to 8-week healing period, all materials supported osteogenesis. CONCLUSIONS: Compared to other materials, the DBM had high osteoinductive properties during the 4- to 8-week time period based on increased mineral content. All materials were associated with immunohistologic evidence of osteogenesis in the rat calvarial defect model.


Assuntos
Subunidade alfa 1 de Fator de Ligação ao Core , Osteogênese , Humanos , Ratos , Animais , Bovinos , Matriz Óssea/química , Matriz Óssea/transplante , Microtomografia por Raio-X , Regeneração Óssea , Minerais/uso terapêutico
14.
Bone Res ; 11(1): 60, 2023 11 09.
Artigo em Inglês | MEDLINE | ID: mdl-37940665

RESUMO

Matrix vesicles (MVs) have shown strong effects in diseases such as vascular ectopic calcification and pathological calcified osteoarthritis and in wound repair of the skeletal system due to their membranous vesicle characteristics and abundant calcium and phosphorus content. However, the role of MVs in the progression of osteoporosis is poorly understood. Here, we report that annexin A5, an important component of the matrix vesicle membrane, plays a vital role in bone matrix homeostasis in the deterioration of osteoporosis. We first identified annexin A5 from adherent MVs but not dissociative MVs of osteoblasts and found that it could be sharply decreased in the bone matrix during the occurrence of osteoporosis based on ovariectomized mice. We then confirmed its potential in mediating the mineralization of the precursor osteoblast lineage via its initial binding with collagen type I to achieve MV adhesion and the subsequent activation of cellular autophagy. Finally, we proved its protective role in resisting bone loss by applying it to osteoporotic mice. Taken together, these data revealed the importance of annexin A5, originating from adherent MVs of osteoblasts, in bone matrix remodeling of osteoporosis and provided a new strategy for the treatment and intervention of bone loss.


Assuntos
Doenças Ósseas Metabólicas , Osteoporose , Calcificação Vascular , Animais , Camundongos , Anexina A5/metabolismo , Calcificação Fisiológica/fisiologia , Matriz Óssea/metabolismo
15.
Biomacromolecules ; 24(12): 5666-5677, 2023 12 11.
Artigo em Inglês | MEDLINE | ID: mdl-37953507

RESUMO

A polysaccharide gel containing covalently bound amikacin, a broad-spectrum antibiotic, was produced by using epichlorohydrin-activated hydroxyethyl starch (HES). The structure of the polymers was analyzed by 13C and 1H nuclear magnetic resonance (13C NMR and 1H NMR) and matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry. The sites of covalent attachment of amikacin to the epoxypropyl substituent and the HES backbone were determined. The antibacterial activity of the polymer was evaluated in vitro using the agar well diffusion method with the Staphylococcus aureus P209 strain. It was demonstrated that the polymer retained activity in the presence of bacterial amylase, which is released upon bacterial attack. The gel was applied for coating pores and surfaces of a biocomposite material based on a xenogenic bovine bone matrix. In vivo experiments showed the effectiveness of utilizing amikacin-containing biocomposite bone-substitute materials in the treatment of experimental osteomyelitis in rats using objective histological control and X-ray tomography.


Assuntos
Amicacina , Matriz Óssea , Ratos , Animais , Bovinos , Amicacina/farmacologia , Staphylococcus aureus , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz/métodos , Amido/farmacologia , Polímeros/química
16.
Sci Rep ; 13(1): 20813, 2023 11 27.
Artigo em Inglês | MEDLINE | ID: mdl-38012303

RESUMO

Osteoclasts uniquely resorb calcified bone matrices. To exert their function, mature osteoclasts maintain the cellular polarity and directional vesicle trafficking to and from the resorbing bone surface. However, the regulatory mechanisms and pathophysiological relevance of these processes remain largely unexplored. Bone histomorphometric analyses in Ccr5-deficient mice showed abnormalities in the morphology and functional phenotype of their osteoclasts, compared to wild type mice. We observed disorganized clustering of nuclei, as well as centrosomes that organize the microtubule network, which was concomitant with impaired cathepsin K secretion in cultured Ccr5-deficient osteoclasts. Intriguingly, forced expression of constitutively active Rho or Rac restored these cytoskeletal phenotypes with recovery of cathepsin K secretion. Furthermore, a gene-disease enrichment analysis identified that PLEKHM1, a responsible gene for osteopetrosis, which regulates lysosomal trafficking in osteoclasts, was regulated by CCR5. These experimental results highlighted that CCR5-mediated signaling served as an intracellular organizer for centrosome clustering in osteoclasts, which was involved in the pathophysiology of bone metabolism.


Assuntos
Reabsorção Óssea , Osteoclastos , Receptores CCR5 , Animais , Camundongos , Osso e Ossos/metabolismo , Matriz Óssea/metabolismo , Reabsorção Óssea/genética , Reabsorção Óssea/metabolismo , Catepsina K/metabolismo , Centrossomo/metabolismo , Osteoclastos/metabolismo , Receptores CCR5/metabolismo
17.
Curr Osteoporos Rep ; 21(6): 787-805, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37897675

RESUMO

PURPOSE OF REVIEW: Metabolic and genetic bone disorders affect not only bone mass but often also the bone material, including degree of mineralization, matrix organization, and lacunar porosity. The quality of juvenile bone is moreover highly influenced by skeletal growth. This review aims to provide a compact summary of the present knowledge on the complex interplay between bone modeling and remodeling during skeletal growth and to alert the reader to the complexity of bone tissue characteristics in children with bone disorders. RECENT FINDINGS: We describe cellular events together with the characteristics of the different tissues and organic matrix organization (cartilage, woven and lamellar bone) occurring during linear growth. Subsequently, we present typical alterations thereof in disorders leading to over-mineralized bone matrix compared to those associated with low or normal mineral content based on bone biopsy studies. Growth spurts or growth retardation might amplify or mask disease-related alterations in bone material, which makes the interpretation of bone tissue findings in children complex and challenging.


Assuntos
Doenças Ósseas , Calcinose , Criança , Humanos , Osso e Ossos , Doenças Ósseas/metabolismo , Matriz Óssea/metabolismo , Densidade Óssea , Calcinose/metabolismo
18.
Biochemistry (Mosc) ; 88(8): 1116-1125, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37758311

RESUMO

High efficiency of hybrid implants based on calcium-magnesium silicate ceramic, diopside, as a carrier of recombinant BMP-2 and xenogenic demineralized bone matrix (DBM) as a scaffold for bone tissue regeneration was demonstrated previously using the model of critical size cranial defects in mice. In order to investigate the possibility of using these implants for growing autologous bone tissue using in vivo bioreactor principle in the patient's own body, effectiveness of ectopic osteogenesis induced by them in intramuscular implantation in mice was studied. At the dose of 7 µg of BMP-2 per implant, dense agglomeration of cells, probably skeletal muscle satellite precursor cells, was observed one week after implantation with areas of intense chondrogenesis, initial stage of indirect osteogenesis, around the implants. After 12 weeks, a dense bone capsule of trabecular structure was formed covered with periosteum and mature bone marrow located in the spaces between the trabeculae. The capsule volume was about 8-10 times the volume of the original implant. There were practically no signs of inflammation and foreign body reaction. Microcomputed tomography data showed significant increase of the relative bone volume, number of trabeculae, and bone tissue density in the group of mice with BMP-2-containing implant in comparison with the group without BMP-2. Considering that DBM can be obtained in practically unlimited quantities with required size and shape, and that BMP-2 is obtained by synthesis in E. coli cells and is relatively inexpensive, further development of the in vivo bioreactor model based on the hybrid implants constructed from BMP-2, diopside, and xenogenic DBM seems promising.


Assuntos
Cálcio , Osteogênese , Camundongos , Humanos , Animais , Matriz Óssea , Microtomografia por Raio-X , Magnésio , Escherichia coli , Proteína Morfogenética Óssea 2/química , Silicatos de Magnésio/análise
19.
Int J Biol Macromol ; 252: 126524, 2023 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-37633545

RESUMO

The irregular expression of bone matrix proteins occurring during the mineralization of bone regeneration results in various deformities which poses a major concern of orthopedic reconstruction. The limitations of the existing reconstruction practice paved a way for the development of a metal-organic composite [TQ-Sr-Fe] with Metal ions strontium [Sr] and iron [Fe] and a biomolecule Thymoquinone [TQ] in an attempt to enhance the bone mineralization due to their positive significance in osteoblast differentiation, proliferation and maturation. TQ-Sr-Fe was synthesized by in-situ coprecipitation and subjected to various characterization to determine their nature, compatibility and osteogenic efficiency. The crystallographic and electron microscopy analysis reveals sheet like structure of the composite. The negative cytotoxicity of TQ-Sr-Fe in the MG 63 cell line signified their biocompatibility. Cell adhesion and proliferation rate affirmed osteoconductive and osteoinductive nature of the composites and it was further supported by the gene expression of osteoblastic differentiation. The sequential expression of bone matrix proteins such as OCN, SPARC, COL 1, and Alkaline Phosphatase elevate the calcium deposition of MG-63 osteoblast like cells and initiates mineralization compared to control. Thus, the metal-organic composite TQ-Sr-Fe would make a suitable composite for accelerating mineralization process which would leads to faster bone regeneration.


Assuntos
Fosfatase Alcalina , Matriz Óssea , Fosfatase Alcalina/metabolismo , Matriz Óssea/metabolismo , Osteogênese/genética , Proteínas , Estrôncio/química , Cálcio/metabolismo
20.
Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi ; 37(8): 945-951, 2023 Aug 15.
Artigo em Chinês | MEDLINE | ID: mdl-37586793

RESUMO

Objective: To measure the concentration of bone morphogenetic protein 2 (BMP-2) in demineralized bone matrix (DBM) prepared from different long bones and to evaluate the osteoinductivity of different DBM on MC3T3-E1 cells. Methods: Different bones from the same cadaver donor were used as the initial materials for making DBM, which were divided into ulna group (uDBM), humerus group (hDBM), tibia group (tDBM), and femur group (fDBM) according to the origins, and boiled DBM (cDBM) was taken as the control group. The proteins of DBM were extracted by guanidine hydrochloride, and the concentrations of BMP-2 were determined by ELISA assay. Then the DBM were co-cultured with MC3T3-E1 cells, the proliferation of MC3T3-E1 cells was observed by cell counting kit 8 (CCK-8) assay. The osteogenic differentiation ability of MC3T3-E1 cells was qualitatively observed by alizarin red, alkaline phosphatase (ALP), and Van Gieson staining, and the osteogenic differentiation ability of MC3T3-E1 cells was quantitatively analyzed by ALP content. Linear regression was used to analyze the effect of BMP-2 concentration in DBM on ALP synthesis. Results: There were significant differences in the concentration of BMP-2 among the DBM groups (P<0.05). The concentrations of BMP-2 in the lower limb long bone were higher than those in the upper limb long bone, and the concentration of BMP-2 in the fDBM group was about 35.5 times that in the uDBM group. CCK-8 assay showed that the cells in each group continued to proliferate within 5 days of co-culture, and the absorbance (A) values at different time points were in the order of cDBM group

Assuntos
Proteína Morfogenética Óssea 2 , Osteogênese , Fosfatase Alcalina , Matriz Óssea , Contagem de Células , Corantes , Animais , Camundongos
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