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1.
Autoimmunity ; 57(1): 2364686, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38946534

RESUMO

BACKGROUND: Chondrocyte viability, apoptosis, and migration are closely related to cartilage injury in osteoarthritis (OA) joints. Exosomes are identified as potential therapeutic agents for OA. OBJECTIVE: This study aimed to investigate the role of exosomes derived from osteocytes in OA, particularly focusing on their effects on cartilage repair and molecular mechanisms. METHODS: An injury cell model was established by treating chondrocytes with IL-1ß. Cartilage repair was evaluated using cell counting kit-8, flow cytometry, scratch test, and Western Blot. Molecular mechanisms were analyzed using quantitative real-time PCR, bioinformatic analysis, and Western Blot. An OA mouse model was established to explore the role of exosomal DLX2 in vivo. RESULTS: Osteocyte-released exosomes promoted cell viability and migration, and inhibited apoptosis and extracellular matrix (ECM) deposition. Moreover, exosomes upregulated DLX2 expression, and knockdown of DLX2 activated the Wnt pathway. Additionally, exosomes attenuated OA in mice by transmitting DLX2. CONCLUSION: Osteocyte-derived exosomal DLX2 alleviated IL-1ß-induced cartilage repair and inactivated the Wnt pathway, thereby alleviating OA progression. The findings suggested that osteocyte-derived exosomes may hold promise as a treatment for OA.


Assuntos
Condrócitos , Exossomos , Proteínas de Homeodomínio , Osteoartrite , Osteócitos , Fatores de Transcrição , Via de Sinalização Wnt , Exossomos/metabolismo , Animais , Osteoartrite/metabolismo , Osteoartrite/patologia , Camundongos , Fatores de Transcrição/metabolismo , Proteínas de Homeodomínio/metabolismo , Proteínas de Homeodomínio/genética , Osteócitos/metabolismo , Condrócitos/metabolismo , Modelos Animais de Doenças , Humanos , Interleucina-1beta/metabolismo , Cartilagem Articular/metabolismo , Cartilagem Articular/patologia , Apoptose , Cartilagem/metabolismo , Cartilagem/patologia , Masculino , Movimento Celular , Sobrevivência Celular
2.
Otol Neurotol ; 45(7): 773-776, 2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-38956760

RESUMO

OBJECTIVE: To review a 3-year case series of endoscopic butterfly inlay cartilage myringoplasty performed by a single surgeon (W.S.K.) and analyze the clinical surgical outcomes. STUDY DESIGN: Retrospective study. SETTING: Tertiary care academic center. PATIENTS: We enrolled 60 ears with tympanic membrane (TM) perforation, receiving endoscopic inlay butterfly myringoplasty between 2019 and 2022. MAIN OUTCOMES AND MEASURES: We reviewed patients' demographics, size and location of TM perforation, operation time, complications, and postoperative pain evaluated by the numerical rating scale (NRS). We analyzed the graft uptake success rate in 5 weeks and the perforation closure rate in 4 months after surgery. We also compared the air-bone gap (ABG) before and after the surgery. RESULTS: Among the 60 ears included, the mean age was 57.0 years, and 78.3% (47 of 60) had small perforations. The average operation time was 48.9 ± 11.5 minutes, and the postoperative NRS was 2.0 ± 1.6. The immediate graft uptake success rate evaluated at postoperative 5 weeks was 96.7% (58 of 60), with myringitis occurring in three ears. Except for 11 patients lost to follow-up, the perforation closure rate evaluated at postoperative 4 months was 100% (49 of 49). The mean ABG significantly improved from preoperative status (8.87 ± 5.51 dB HL) to postoperative 4 months (6.22 ± 6.03 dB HL) ( p = 0.019). CONCLUSIONS: A single surgeon's success rate for endoscopic butterfly inlay cartilage myringoplasty was almost 100%. This surgical procedure is safe and effective, with a high graft success rate.


Assuntos
Endoscopia , Miringoplastia , Perfuração da Membrana Timpânica , Humanos , Perfuração da Membrana Timpânica/cirurgia , Miringoplastia/métodos , Feminino , Pessoa de Meia-Idade , Masculino , Estudos Retrospectivos , Endoscopia/métodos , Resultado do Tratamento , Adulto , Idoso , Cartilagem/transplante
3.
Life Sci Alliance ; 7(9)2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38981683

RESUMO

Collagenopathies are a group of clinically diverse disorders caused by defects in collagen folding and secretion. For example, mutations in the gene encoding collagen type-II, the primary collagen in cartilage, can lead to diverse chondrodysplasias. One example is the Gly1170Ser substitution in procollagen-II, which causes precocious osteoarthritis. Here, we biochemically and mechanistically characterize an induced pluripotent stem cell-based cartilage model of this disease, including both hetero- and homozygous genotypes. We show that Gly1170Ser procollagen-II is notably slow to fold and secrete. Instead, procollagen-II accumulates intracellularly, consistent with an endoplasmic reticulum (ER) storage disorder. Likely owing to the unique features of the collagen triple helix, this accumulation is not recognized by the unfolded protein response. Gly1170Ser procollagen-II interacts to a greater extent than wild-type with specific ER proteostasis network components, consistent with its slow folding. These findings provide mechanistic elucidation into the etiology of this disease. Moreover, the easily expandable cartilage model will enable rapid testing of therapeutic strategies to restore proteostasis in the collagenopathies.


Assuntos
Colágeno Tipo II , Retículo Endoplasmático , Pró-Colágeno , Resposta a Proteínas não Dobradas , Retículo Endoplasmático/metabolismo , Humanos , Pró-Colágeno/metabolismo , Colágeno Tipo II/metabolismo , Mutação , Células-Tronco Pluripotentes Induzidas/metabolismo , Cartilagem/metabolismo , Cartilagem/patologia , Dobramento de Proteína , Artrite/metabolismo , Artrite/genética , Osteoartrite/metabolismo , Osteoartrite/genética , Osteoartrite/patologia , Animais , Condrócitos/metabolismo
4.
Sci Rep ; 14(1): 15022, 2024 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-38951570

RESUMO

Cartilage tissue engineering aims to develop functional substitutes for treating cartilage defects and osteoarthritis. Traditional two-dimensional (2D) cell culture systems lack the complexity of native cartilage, leading to the development of 3D regenerative cartilage models. In this study, we developed a 3D model using Gelatin Methacryloyl (GelMA)-based hydrogels seeded with Y201 cells, a bone marrow mesenchymal stem cell line. The model investigated chondrogenic differentiation potential in response to Wnt3a stimulation within the GelMA scaffold and validated using known chondrogenic agonists. Y201 cells demonstrated suitability for the model, with increased proteoglycan content and upregulated chondrogenic marker expression under chondrogenic conditions. Wnt3a enhanced cell proliferation, indicating activation of the Wnt/ß-catenin pathway, which plays a role in cartilage development. GelMA hydrogels provided an optimal scaffold, supporting cell viability and proliferation. The 3D model exhibited consistent responses to chondrogenic agonists, with TGF-ß3 enhancing cartilage-specific extracellular matrix (ECM) production and chondrogenic differentiation. The combination of Wnt3a and TGF-ß3 showed synergistic effects, promoting chondrogenic differentiation and ECM production. This study presents a 3D regenerative cartilage model with potential for investigating cartilage biology, disease mechanisms, and drug screening. The model provides insights into complex cartilage regeneration mechanisms and offers a platform for developing therapeutic approaches for cartilage repair and osteoarthritis treatment.


Assuntos
Diferenciação Celular , Proliferação de Células , Condrogênese , Hidrogéis , Células-Tronco Mesenquimais , Engenharia Tecidual , Proteína Wnt3A , Proteína Wnt3A/metabolismo , Condrogênese/efeitos dos fármacos , Engenharia Tecidual/métodos , Proliferação de Células/efeitos dos fármacos , Hidrogéis/química , Células-Tronco Mesenquimais/metabolismo , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/efeitos dos fármacos , Humanos , Cartilagem/metabolismo , Gelatina/química , Alicerces Teciduais/química , Fator de Crescimento Transformador beta3/metabolismo , Fator de Crescimento Transformador beta3/farmacologia , Linhagem Celular , Matriz Extracelular/metabolismo , Via de Sinalização Wnt/efeitos dos fármacos , Condrócitos/metabolismo , Condrócitos/citologia , Animais
5.
J Morphol ; 285(7): e21747, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38956884

RESUMO

Using histological cross-sections, the chondrocranium anatomy was reconstructed for two developmental stages of Hermann's tortoise (Testudo hermanni). The morphology differs from the chondrocrania of most other turtles by a process above the ectochoanal cartilage with Pelodiscus sinensis being the only other known species with such a structure. The anterior and posterior processes of the tectum synoticum are better developed than in most other turtles and an ascending process of the palatoquadrate is missing, which is otherwise only the case in pleurodiran turtles. The nasal region gets proportionally larger during development. We interpret the enlargement of the nasal capsules as an adaption to increase the surface area of the olfactory epithelium for better perception of volant odors. Elongation of the nasal capsules in trionychids, in contrast, is unlikely to be related to olfaction, while it is ambiguous in the case of Sternotherus odoratus. However, we have to conclude that research on chondrocranium anatomy is still at its beginning and more comprehensive detailed descriptions in relation to other parts of the anatomy are needed before providing broad-scale ecological and phylogenetic interpretations.


Assuntos
Tartarugas , Animais , Tartarugas/anatomia & histologia , Crânio/anatomia & histologia , Cartilagem/anatomia & histologia
6.
Stem Cell Res Ther ; 15(1): 177, 2024 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-38886785

RESUMO

BACKGROUND: Cartilage is a kind of avascular tissue, and it is difficult to repair itself when it is damaged. In this study, we investigated the regulation of chondrogenic differentiation and vascular formation in human jaw bone marrow mesenchymal stem cells (h-JBMMSCs) by the long-chain noncoding RNA small nucleolar RNA host gene 1 (SNHG1) during cartilage tissue regeneration. METHODS: JBMMSCs were isolated from the jaws via the adherent method. The effects of lncRNA SNHG1 on the chondrogenic differentiation of JBMMSCs in vitro were detected by real-time fluorescence quantitative polymerase chain reaction (RT-qPCR), Pellet experiment, Alcian blue staining, Masson's trichrome staining, and modified Sirius red staining. RT-qPCR, matrix gel tube formation, and coculture experiments were used to determine the effect of lncRNA SNHG1 on the angiogenesis in JBMMSCs in vitro. A model of knee cartilage defects in New Zealand rabbits and a model of subcutaneous matrix rubber suppositories in nude mice were constructed for in vivo experiments. Changes in mitochondrial function were detected via RT-qPCR, dihydroethidium (DHE) staining, MitoSOX staining, tetramethyl rhodamine methyl ester (TMRM) staining, and adenosine triphosphate (ATP) detection. Western blotting was used to detect the phosphorylation level of signal transducer and activator of transcription 3 (STAT3). RESULTS: Alcian blue staining, Masson's trichrome staining, and modified Sirius Red staining showed that lncRNA SNHG1 promoted chondrogenic differentiation. The lncRNA SNHG1 promoted angiogenesis in vitro and the formation of microvessels in vivo. The lncRNA SNHG1 promoted the repair and regeneration of rabbit knee cartilage tissue. Western blot and alcian blue staining showed that the JAK inhibitor reduced the increase of STAT3 phosphorylation level and staining deepening caused by SNHG1. Mitochondrial correlation analysis revealed that the lncRNA SNHG1 led to a decrease in reactive oxygen species (ROS) levels, an increase in mitochondrial membrane potential and an increase in ATP levels. Alcian blue staining showed that the ROS inhibitor significantly alleviated the decrease in blue fluorescence caused by SNHG1 knockdown. CONCLUSIONS: The lncRNA SNHG1 promotes chondrogenic differentiation and angiogenesis of JBMMSCs. The lncRNA SNHG1 regulates the phosphorylation of STAT3, reduces the level of ROS, regulates mitochondrial energy metabolism, and ultimately promotes cartilage regeneration.


Assuntos
Diferenciação Celular , Condrogênese , Células-Tronco Mesenquimais , Mitocôndrias , RNA Longo não Codificante , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Humanos , Animais , Coelhos , Mitocôndrias/metabolismo , Células-Tronco Mesenquimais/metabolismo , Células-Tronco Mesenquimais/citologia , Condrogênese/genética , Camundongos , Camundongos Nus , Regeneração , Neovascularização Fisiológica , Cartilagem/metabolismo , Fator de Transcrição STAT3/metabolismo , Fator de Transcrição STAT3/genética , Angiogênese
7.
Int J Mol Sci ; 25(11)2024 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-38891883

RESUMO

Articular cartilage damage still remains a major problem in orthopedical surgery. The development of tissue engineering techniques such as autologous chondrocyte implantation is a promising way to improve clinical outcomes. On the other hand, the clinical application of autologous chondrocytes has considerable limitations. Mesenchymal stromal cells (MSCs) from various tissues have been shown to possess chondrogenic differentiation potential, although to different degrees. In the present study, we assessed the alterations in chondrogenesis-related gene transcription rates and extracellular matrix deposition levels before and after the chondrogenic differentiation of MSCs in a 3D spheroid culture. MSCs were obtained from three different tissues: umbilical cord Wharton's jelly (WJMSC-Wharton's jelly mesenchymal stromal cells), adipose tissue (ATMSC-adipose tissue mesenchymal stromal cells), and the dental pulp of deciduous teeth (SHEDs-stem cells from human exfoliated deciduous teeth). Monolayer MSC cultures served as baseline controls. Newly formed 3D spheroids composed of MSCs previously grown in 2D cultures were precultured for 2 days in growth medium, and then, chondrogenic differentiation was induced by maintaining them in the TGF-ß1-containing medium for 21 days. Among the MSC types studied, WJMSCs showed the most similarities with primary chondrocytes in terms of the upregulation of cartilage-specific gene expression. Interestingly, such upregulation occurred to some extent in all 3D spheroids, even prior to the addition of TGF-ß1. These results confirm that the potential of Wharton's jelly is on par with adipose tissue as a valuable cell source for cartilage engineering applications as well as for the treatment of osteoarthritis. The 3D spheroid environment on its own acts as a trigger for the chondrogenic differentiation of MSCs.


Assuntos
Diferenciação Celular , Condrócitos , Condrogênese , Matriz Extracelular , Células-Tronco Mesenquimais , Esferoides Celulares , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/metabolismo , Humanos , Condrogênese/genética , Matriz Extracelular/metabolismo , Esferoides Celulares/citologia , Esferoides Celulares/metabolismo , Condrócitos/citologia , Condrócitos/metabolismo , Células Cultivadas , Geleia de Wharton/citologia , Tecido Adiposo/citologia , Tecido Adiposo/metabolismo , Técnicas de Cultura de Células/métodos , Engenharia Tecidual/métodos , Cartilagem/citologia , Cartilagem/metabolismo , Dente Decíduo/citologia , Dente Decíduo/metabolismo , Polpa Dentária/citologia , Polpa Dentária/metabolismo
8.
J Morphol ; 285(7): e21745, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38877975

RESUMO

The jaws and their supporting cartilages are tessellated in elasmobranchs and exhibit an abrupt increase in stiffness under compression. The major jaw-supporting cartilage, the hyomandibula, varies widely by shape and size and the extent of the load-bearing role is hypothesized to be inversely related to the number of craniopalatine articulations. Here, we test this hypothesis by evaluating the strength of the hyomandibular cartilage under compression in 13 species that represent all four jaw suspension systems in elasmobranchs (amphistyly, orbitostyly, hyostyly, and euhyostyly). The strength of the hyomandibular cartilages was measured directly using a material testing machine under compressive load, and indirectly by measuring morphological variables putatively associated with strength. The first measure of strength is force to yield (Fy), which was the peak force (N) exerted on the hyomandibula before plastic deformation. The second measure was compressive yield strength (σy, also called yield stress), which is calculated as peak force (N) before plastic deformation/cross-sectional area (mm2) of the specimen. Our results show that the load-bearing role of the hyomandibular cartilage, as measured by yield strength, is inversely related to the number of craniopalatine articulations, as predicted. Force to yield was lower for euhyostylic jaw suspensions and similar for the others. We also found that mineralization is associated with greater yield strength, while the second moment of area is associated with greater force to yield.


Assuntos
Cartilagem , Elasmobrânquios , Arcada Osseodentária , Animais , Arcada Osseodentária/anatomia & histologia , Arcada Osseodentária/fisiologia , Elasmobrânquios/fisiologia , Elasmobrânquios/anatomia & histologia , Cartilagem/fisiologia , Força Compressiva/fisiologia , Fenômenos Biomecânicos , Estresse Mecânico
9.
Sci Data ; 11(1): 626, 2024 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-38871782

RESUMO

The chondrocranium provides the key initial support for the fetal brain, jaws and cranial sensory organs in all vertebrates. The patterns of shaping and growth of the chondrocranium set up species-specific development of the entire craniofacial complex. The 3D development of chondrocranium have been studied primarily in animal model organisms, such as mice or zebrafish. In comparison, very little is known about the full 3D human chondrocranium, except from drawings made by anatomists many decades ago. The knowledge of human-specific aspects of chondrocranial development are essential for understanding congenital craniofacial defects and human evolution. Here advanced microCT scanning was used that includes contrast enhancement to generate the first 3D atlas of the human fetal chondrocranium during the middle trimester (13 to 19 weeks). In addition, since cartilage and bone are both visible with the techniques used, the  endochondral ossification of cranial base was mapped since this region is so critical for brain and jaw growth. The human 3D models are published as a scientific resource for human development.


Assuntos
Imageamento Tridimensional , Humanos , Feto/diagnóstico por imagem , Feminino , Microtomografia por Raio-X , Crânio/diagnóstico por imagem , Crânio/embriologia , Gravidez , Cartilagem/diagnóstico por imagem , Cartilagem/embriologia
10.
Int J Biol Macromol ; 272(Pt 1): 132848, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38830491

RESUMO

Collagen-based (COL) hydrogels could be a promising treatment option for injuries to the articular cartilage (AC) becuase of their similarity to AC native extra extracellular matrix. However, the high hydration of COL hydrogels poses challenges for AC's mechanical properties. To address this, we developed a hydrogel platform that incorporating cellulose nanocrystals (CNCs) within COL and followed by plastic compression (PC) procedure to expel the excessive fluid out. This approach significantly improved the mechanical properties of the hydrogels and enhanced the chondrogenic differentiation of mesenchymal stem cells (MSCs). Radially confined PC resulted in higher collagen fibrillar densities together with reducing fibril-fibril distances. Compressed hydrogels containing CNCs exhibited the highest compressive modulus and toughness. MSCs encapsulated in these hydrogels were initially affected by PC, but their viability improved after 7 days. Furthermore, the morphology of the cells and their secretion of glycosaminoglycans (GAGs) were positively influenced by the compressed COL-CNC hydrogel. Our findings shed light on the combined effects of PC and CNCs in improving the physical and mechanical properties of COL and their role in promoting chondrogenesis.


Assuntos
Diferenciação Celular , Celulose , Condrogênese , Colágeno , Hidrogéis , Células-Tronco Mesenquimais , Nanopartículas , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/efeitos dos fármacos , Células-Tronco Mesenquimais/metabolismo , Celulose/química , Celulose/farmacologia , Condrogênese/efeitos dos fármacos , Diferenciação Celular/efeitos dos fármacos , Nanopartículas/química , Colágeno/química , Colágeno/farmacologia , Hidrogéis/química , Hidrogéis/farmacologia , Animais , Plásticos/química , Plásticos/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Glicosaminoglicanos/metabolismo , Cartilagem/citologia , Cartilagem/efeitos dos fármacos
11.
Clin Biomech (Bristol, Avon) ; 116: 106269, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38861874

RESUMO

BACKGROUND: Slipped capital femoral epiphysis is a prevalent pediatric hip disorder. Recent studies suggest the spine's sagittal profile may influence the proximal femoral growth plate's slippage, an aspect not extensively explored. This study utilizes finite element analysis to investigate how various spinopelvic alignments affect shear stress and growth plate slip. METHODS: A finite element model was developed from CT scans of a healthy adult male lumbar spine, pelvis, and femurs. The model was subjected to various sagittal alignments through reorientation. Simulations of two-leg stance, one-leg stance, walking heel strike, ascending stairs heel strike, and descending stairs heel strike were conducted. Parameters measured included hip joint contact area, stress, and maximum growth plate Tresca (shear) stress. FINDINGS: Posterior pelvic tilt cases indicated larger shear stresses compared to the anterior pelvic tilt variants except in two leg stance. Two leg stance resulted in decreases in the posterior tilted pelvi variants hip contact and growth plate Tresca stress compared to anterior tilted pelvi, however a combination of posterior pelvic tilt and high pelvic incidence indicated larger shear stresses on the growth plate. One leg stance and heal strike resulted in higher shear stress on the growth plate in posterior pelvic tilt variants compared to anterior pelvic tilt, with a combination of posterior pelvic tilt and high pelvic incidence resulting in the largest shear. INTERPRETATION: Our findings suggest that posterior pelvic tilt and high pelvic incidence may lead to increased shear stress at the growth plate. Activities performed in patients with these alignments may predispose to biomechanical loading that shears the growth plate, potentially leading to slip.


Assuntos
Análise de Elementos Finitos , Pelve , Humanos , Masculino , Pelve/diagnóstico por imagem , Cabeça do Fêmur/diagnóstico por imagem , Cabeça do Fêmur/fisiopatologia , Estresse Mecânico , Escorregamento das Epífises Proximais do Fêmur/fisiopatologia , Escorregamento das Epífises Proximais do Fêmur/diagnóstico por imagem , Adulto , Simulação por Computador , Articulação do Quadril/fisiopatologia , Articulação do Quadril/diagnóstico por imagem , Fêmur/diagnóstico por imagem , Fêmur/fisiopatologia , Lâmina de Crescimento/diagnóstico por imagem , Lâmina de Crescimento/fisiopatologia , Lâmina de Crescimento/fisiologia , Cartilagem/diagnóstico por imagem , Modelos Biológicos , Fenômenos Biomecânicos , Postura/fisiologia , Coluna Vertebral/diagnóstico por imagem , Coluna Vertebral/fisiopatologia , Coluna Vertebral/fisiologia
12.
J Mater Chem B ; 12(25): 6242-6256, 2024 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-38842217

RESUMO

Designing artificial nano-enzymes for scavenging reactive oxygen species (ROS) in chondrocytes (CHOs) is considered the most feasible pathway for the treatment of osteoarthritis (OA). However, the accumulation of ROS due to the amount of nano-enzymatic catalytic site exposure and insufficient oxygen supply seriously threatens the clinical application of this therapy. Although metal-organic framework (MOF) immobilization of artificial nano-enzymes to enhance active site exposure has been extensively studied, artificial nano-enzymes/MOFs for ROS scavenging in OA treatment are still lacking. In this study, a biocompatible lubricating hydrogel-loaded iron-doped zeolitic imidazolate framework-8 (Fe/ZIF-8/Gel) centrase was engineered to scavenge endogenous overexpressed ROS synergistically generating dissolved oxygen and enhancing sustained lubrication for CHOs as a ternary artificial nano-enzyme. This property enabled the nano-enzymatic hydrogels to mitigate OA hypoxia and inhibit oxidative stress damage successfully. Ternary strategy-based therapies show excellent cartilage repair in vivo. The experimental results suggest that nano-enzyme-enhanced lubricating hydrogels are a potentially effective OA treatment and a novel strategy.


Assuntos
Condrócitos , Hidrogéis , Espécies Reativas de Oxigênio , Hidrogéis/química , Hidrogéis/farmacologia , Animais , Condrócitos/metabolismo , Condrócitos/efeitos dos fármacos , Condrócitos/citologia , Espécies Reativas de Oxigênio/metabolismo , Estruturas Metalorgânicas/química , Estruturas Metalorgânicas/farmacologia , Osteoartrite/tratamento farmacológico , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Cartilagem/efeitos dos fármacos , Cartilagem/metabolismo , Tamanho da Partícula , Humanos , Zeolitas/química
13.
Stem Cell Res Ther ; 15(1): 183, 2024 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-38902814

RESUMO

In the realm of studying joint-related diseases, there is a continuous quest for more accurate and representative models. Recently, regenerative medicine and tissue engineering have seen a growing interest in utilizing organoids as powerful tools for studying complex biological systems in vitro. Organoids, three-dimensional structures replicating the architecture and function of organs, provide a unique platform for investigating disease mechanisms, drug responses, and tissue regeneration. The surge in organoid research is fueled by the need for physiologically relevant models to bridge the gap between traditional cell cultures and in vivo studies. Osteochondral organoids have emerged as a promising avenue in this pursuit, offering a better platform to mimic the intricate biological interactions within bone and cartilage. This review explores the significance of osteochondral organoids and the need for their development in advancing our understanding and treatment of bone and cartilage-related diseases. It summarizes osteochondral organoids' insights and research progress, focusing on their composition, materials, cell sources, and cultivation methods, as well as the concept of organoids on chips and application scenarios. Additionally, we address the limitations and challenges these organoids face, emphasizing the necessity for further research to overcome these obstacles and facilitate orthopedic regeneration.


Assuntos
Organoides , Engenharia Tecidual , Organoides/citologia , Organoides/metabolismo , Humanos , Engenharia Tecidual/métodos , Animais , Cartilagem/citologia , Medicina Regenerativa/métodos , Osso e Ossos/citologia , Osso e Ossos/fisiologia
15.
Int J Biol Macromol ; 273(Pt 2): 133217, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38897519

RESUMO

Recent research focuses on fabricating scaffolds imitating the extracellular matrix (ECM) in texture, composition, and functionality. Moreover, specific nano-bio-particles can enhance cell differentiation. Decellularized ECM nanoparticles possess all of the mentioned properties. In this research, cartilage ECM, extracted from the cow's femur condyle, was decellularized, and ECM nanoparticles were synthesized. Finally, nanocomposite electrospun fibers containing polyhydroxybutyrate (PHB), chitosan (Cs) nanoparticles, and ECM nanoparticles were fabricated and characterized. TEM and DLS results revealed ECM nanoparticle sizes of 17.51 and 21.6 nm, respectively. Optimal performance was observed in the scaffold with 0.75 wt% ECM nanoparticles (PHB-Cs/0.75E). By adding 0.75 wt% ECM, the ultimate tensile strength and elongation at break increased by about 29 % and 21 %, respectively, while the water contact angle and crystallinity decreased by about 36° and 2 %, respectively. Uneven and rougher surfaces of the PHB-Cs/0.75E were determined by FESEM and AFM images, respectively. TEM images verified the uniform dispersion of nanoparticles within the fibers. After 70 days of degradation in PBS, the PHB-Cs/0.75E and PHB-Cs scaffolds demonstrated insignificant weight loss differences. Eventually, enhanced viability, attachment, and proliferation of the human costal chondrocytes on the PHB-Cs/0.75E scaffold, concluded from MTT, SEM, and DAPI staining, confirmed its potential for cartilage tissue engineering.


Assuntos
Cartilagem , Quitosana , Matriz Extracelular , Hidroxibutiratos , Nanopartículas , Engenharia Tecidual , Alicerces Teciduais , Quitosana/química , Engenharia Tecidual/métodos , Alicerces Teciduais/química , Matriz Extracelular/química , Matriz Extracelular/metabolismo , Nanopartículas/química , Animais , Hidroxibutiratos/química , Cartilagem/citologia , Cartilagem/metabolismo , Poliésteres/química , Humanos , Bovinos , Condrócitos/citologia , Condrócitos/metabolismo , Poli-Hidroxibutiratos
16.
Int J Biol Macromol ; 273(Pt 1): 132819, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38830498

RESUMO

The avascular nature of hyaline cartilage results in limited spontaneous self-repair and regenerative capabilities when damaged. Recent advances in three-dimensional bioprinting have enabled the precise dispensing of cell-laden biomaterials, commonly referred to as 'bioinks', which are emerging as promising solutions for tissue regeneration. An effective bioink for cartilage tissue engineering needs to create a micro-environment that promotes cell differentiation and supports neocartilage tissue formation. In this study, we introduced an innovative bioink composed of photocurable acrylated type I collagen (COLMA), thiol-modified hyaluronic acid (THA), and poly(ethylene glycol) diacrylate (PEGDA) for 3D bioprinting cartilage grafts using human nasal chondrocytes. Both collagen and hyaluronic acid, being key components of the extracellular matrix (ECM) in the human body, provide essential biological cues for tissue regeneration. We evaluated three formulations - COLMA, COLMA+THA, and COLMA+THA+PEGDA - for their printability, cell viability, structural integrity, and capabilities in forming cartilage-like ECM. The addition of THA and PEGDA significantly enhanced these properties, showcasing the potential of this bioink in advancing applications in cartilage repair and reconstructive surgery.


Assuntos
Ácido Hialurônico , Engenharia Tecidual , Alicerces Teciduais , Ácido Hialurônico/química , Ácido Hialurônico/farmacologia , Engenharia Tecidual/métodos , Humanos , Alicerces Teciduais/química , Condrócitos/citologia , Condrócitos/efeitos dos fármacos , Polietilenoglicóis/química , Bioimpressão/métodos , Colágeno/química , Impressão Tridimensional , Cartilagem/citologia , Matriz Extracelular/química , Sobrevivência Celular/efeitos dos fármacos , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Tinta
17.
Otol Neurotol ; 45(6): 671-675, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38865726

RESUMO

OBJECTIVE: To analyze the outcomes of exoscopic versus microscopic type 1 tympanoplasty. STUDY DESIGN: Retrospective chart review. SETTING: Tertiary care otology-neurotology practice. PATIENTS: Adult subjects with a diagnosis of tympanic membrane perforation from 2018 to 2022. INTERVENTION: Exoscopic or microscopic tympanoplasty with cartilage + perichondrium or perichondrium/fascia graft. MAIN OUTCOME MEASURES: Primary outcomes were graft success rate (1 wk, 3 wk, 3 mo, and 6 mo postoperatively) and operative time. Secondary outcomes included audiometric outcomes of postoperative air-bone gap (ABG), change in ABG, pure tone average (PTA), speech reception threshold (SRT), and word recognition score (WRS) at 6-month follow-up and complication rates of cerebrospinal fluid leak, facial nerve injury, persistent tinnitus, and persistent vertigo. RESULTS: Seventy-one patients underwent type 1 tympanoplasty by a single surgeon. Thirty-six patients underwent exoscopic tympanoplasty, and 35 patients underwent microscopic tympanoplasty. Cartilage and perichondrium were utilized in 27 subjects (75.0%) in the exoscopic group and in 25 subjects (71.4%) in the microscopic group (p = 0.7, Cramer's V = 0.04). Graft success rate was as follows (exoscope versus microscope): 100% (36/36) versus 100% (35/35) at 1 week (p = 1.0, Cramer's V = 0.0), 97.2% (35/36) versus 100% (35/35) at 3 weeks (p = 1.0, Cramer's V = 0.1), 97.2% (35/36) versus 94.3% (33/35) at 3 months (p = 1.0, Cramer's V = 0.07), and 91.7% (33/36) versus 91.4% (32/35) at 6 months (p = 0.7, Cramer's V = 0.0). Operative time was 57.7 minutes for the exoscopic group and 65.4 minutes for the microscopic group (p = 0.08, 95% CI [-16.4, 0.9], Cohen's d = 0.4). There were no serious complications. All preoperative and postoperative audiometric outcomes were comparable. CONCLUSIONS: The outcomes after exoscopic versus microscopic type 1 tympanoplasty are comparable.


Assuntos
Perfuração da Membrana Timpânica , Timpanoplastia , Humanos , Timpanoplastia/métodos , Masculino , Feminino , Adulto , Perfuração da Membrana Timpânica/cirurgia , Estudos Retrospectivos , Pessoa de Meia-Idade , Resultado do Tratamento , Microcirurgia/métodos , Idoso , Audiometria de Tons Puros , Cartilagem , Complicações Pós-Operatórias/epidemiologia
18.
Rev Med Suisse ; 20(878): 1173-1177, 2024 Jun 12.
Artigo em Francês | MEDLINE | ID: mdl-38867563

RESUMO

Complex ear reconstruction requires specialized multidisciplinary care. Most patients present with microtia, often associated with hearing disorders. The management of these disorders is a priority, and reconstruction of the external ear remains optional. Nowadays, auricular reconstruction is based on the subcutaneous implantation of either autologous cartilage or an allogeneic implant. Autologous reconstruction requires highly specialized surgical expertise and involves harvesting rib cartilage but carries a lower risk of exposure compared to allogeneic implants. Both techniques yield good results with a high success rate and have a positive impact on the social functioning and daily life of patients.


La reconstruction complexe du pavillon auriculaire nécessite une prise en charge multidisciplinaire spécialisée. La majorité des patients nécessitant ce geste présentent une microtie, souvent associée à des troubles de l'audition. La prise en charge de ceux-ci est prioritaire et la reconstruction du pavillon reste facultative. Aujourd'hui, la reconstruction du pavillon se base sur l'implantation sous-cutanée d'une maquette de cartilage autologue ou d'un implant allogène. La reconstruction autologue demande une expertise chirurgicale hautement spécialisée et nécessite un prélèvement de cartilage costal mais présente un risque d'exposition inférieur par rapport à l'implant allogène. Les deux techniques permettent d'atteindre de bons résultats avec un taux de réussite élevé et un effet positif sur le fonctionnement social et le quotidien des patients.


Assuntos
Procedimentos de Cirurgia Plástica , Humanos , Procedimentos de Cirurgia Plástica/métodos , Orelha Externa/anormalidades , Orelha Externa/cirurgia , Microtia Congênita/cirurgia , Microtia Congênita/terapia , Transplante Autólogo/métodos , Cartilagem/transplante , Próteses e Implantes
19.
Int J Mol Sci ; 25(9)2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38732122

RESUMO

Osteoarthritis is more prevalent than any other form of arthritis and is characterized by the progressive mechanical deterioration of joints. Glucosamine, an amino monosaccharide, has been used for over fifty years as a dietary supplement to alleviate osteoarthritis-related discomfort. Silibinin, extracted from milk thistle, modifies the degree of glycosylation of target proteins, making it an essential component in the treatment of various diseases. In this study, we aimed to investigate the functional roles of glucosamine and silibinin in cartilage homeostasis using the TC28a2 cell line. Western blots showed that glucosamine suppressed the N-glycosylation of the gp130, EGFR, and N-cadherin proteins. Furthermore, both glucosamine and silibinin differentially decreased and increased target proteins such as gp130, Snail, and KLF4 in TC28a2 cells. We observed that both compounds dose-dependently induced the proliferation of TC28a2 cells. Our MitoSOX and DCFH-DA dye data showed that 1 µM glucosamine suppressed mitochondrial reactive oxygen species (ROS) generation and induced cytosol ROS generation, whereas silibinin induced both mitochondrial and cytosol ROS generation in TC28a2 cells. Our JC-1 data showed that glucosamine increased red aggregates, resulting in an increase in the red/green fluorescence intensity ratio, while all the tested silibinin concentrations increased the green monomers, resulting in decreases in the red/green ratio. We observed increasing subG1 and S populations and decreasing G1 and G2/M populations with increasing amounts of glucosamine, while increasing amounts of silibinin led to increases in subG1, S, and G2/M populations and decreases in G1 populations in TC28a2 cells. MTT data showed that both glucosamine and silibinin induced cytotoxicity in TC28a2 cells in a dose-dependent manner. Regarding endoplasmic reticulum stress, both compounds induced the expression of CHOP and increased the level of p-eIF2α/eIF2α. With respect to O-GlcNAcylation status, glucosamine and silibinin both reduced the levels of O-GlcNAc transferase and hypoxia-inducible factor 1 alpha. Furthermore, we examined proteins and mRNAs related to these processes. In summary, our findings demonstrated that these compounds differentially modulated cellular proliferation, mitochondrial and cytosol ROS generation, the mitochondrial membrane potential, the cell cycle profile, and autophagy. Therefore, we conclude that glucosamine and silibinin not only mediate glycosylation modifications but also regulate cellular processes in human chondrocytes.


Assuntos
Condrócitos , Glucosamina , Homeostase , Fator 4 Semelhante a Kruppel , Espécies Reativas de Oxigênio , Silibina , Glucosamina/farmacologia , Glucosamina/metabolismo , Humanos , Silibina/farmacologia , Glicosilação/efeitos dos fármacos , Condrócitos/metabolismo , Condrócitos/efeitos dos fármacos , Homeostase/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Fator 4 Semelhante a Kruppel/metabolismo , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Mitocôndrias/metabolismo , Mitocôndrias/efeitos dos fármacos , Cartilagem/metabolismo , Cartilagem/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Osteoartrite/metabolismo , Osteoartrite/tratamento farmacológico
20.
J Biomech ; 169: 112131, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38739987

RESUMO

Cartilage endplates (CEPs) act as protective mechanical barriers for intervertebral discs (IVDs), yet their heterogeneous structure-function relationships are poorly understood. This study addressed this gap by characterizing and correlating the regional biphasic mechanical properties and biochemical composition of human lumbar CEPs. Samples from central, lateral, anterior, and posterior portions of the disc (n = 8/region) were mechanically tested under confined compression to quantify swelling pressure, equilibrium aggregate modulus, and hydraulic permeability. These properties were correlated with CEP porosity and glycosaminoglycan (s-GAG) content, which were obtained by biochemical assays of the same specimens. Both swelling pressure (142.79 ± 85.89 kPa) and aggregate modulus (1864.10 ± 1240.99 kPa) were found to be regionally dependent (p = 0.0001 and p = 0.0067, respectively) in the CEP and trended lowest in the central location. No significant regional dependence was observed for CEP permeability (1.35 ± 0.97 * 10-16 m4/Ns). Porosity measurements correlated significantly with swelling pressure (r = -0.40, p = 0.0227), aggregate modulus (r = -0.49, p = 0.0046), and permeability (r = 0.36, p = 0.0421), and appeared to be the primary indicator of CEP biphasic mechanical properties. Second harmonic generation microscopy also revealed regional patterns of collagen fiber anchoring, with fibers inserting the CEP perpendicularly in the central region and at off-axial directions in peripheral regions. These results suggest that CEP tissue has regionally dependent mechanical properties which are likely due to the regional variation in porosity and matrix structure. This work advances our understanding of healthy baseline endplate biomechanics and lays a groundwork for further understanding the role of CEPs in IVD degeneration.


Assuntos
Disco Intervertebral , Vértebras Lombares , Humanos , Vértebras Lombares/fisiologia , Disco Intervertebral/fisiologia , Pessoa de Meia-Idade , Masculino , Feminino , Porosidade , Adulto , Idoso , Glicosaminoglicanos/metabolismo , Fenômenos Biomecânicos , Cartilagem/fisiologia , Estresse Mecânico
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