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1.
Int J Mol Sci ; 22(6)2021 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-33802838

RESUMO

Osteoarthritis (OA) is a multifactorial disease which is characterized by a change in the homeostasis of the extracellular matrix (ECM). The ECM is essential for the function of the articular cartilage and plays an important role in cartilage mechanotransduction. To provide a better understanding of the interaction between the ECM and the actin cytoskeleton, we investigated the localization and expression of the Ca2+-dependent proteins cartilage oligomeric matrix protein (COMP), thrombospondin-1 (TSP-1), plastin 3 (PLS3) and stromal interaction molecule 1 (STIM1). We investigated 16 patients who suffered from varus knee OA and performed a topographical analysis of the cartilage from the medial and lateral compartment of the proximal tibial plateau. In a varus knee, OA is more pronounced in the medial compared to the lateral compartment as a result of an overloading due to the malalignment. We detected a location-dependent staining of PLS3 and STIM1 in the articular cartilage tissue. The staining intensity for both proteins correlated with the degree of cartilage degeneration. The staining intensity of TSP-1 was clearly reduced in the cartilage of the more affected medial compartment, an observation that was confirmed in cartilage extracts by immunoblotting. The total amount of COMP was unchanged; however, slight changes were detected in the localization of the protein. Our results provide novel information on alterations in OA cartilage suggesting that Ca2+-dependent mechanotransduction between the ECM and the actin cytoskeleton might play an essential role in the pathomechanism of OA.


Assuntos
Cartilagem Articular/metabolismo , Articulação do Joelho/metabolismo , Glicoproteínas de Membrana/metabolismo , Proteínas dos Microfilamentos/metabolismo , Osteoartrite do Joelho/metabolismo , Molécula 1 de Interação Estromal/metabolismo , Trombospondinas/metabolismo , Idoso , Idoso de 80 Anos ou mais , Proteína de Matriz Oligomérica de Cartilagem/metabolismo , Condrócitos/metabolismo , Feminino , Humanos , Articulação do Joelho/patologia , Masculino , Pessoa de Meia-Idade , Osteoartrite do Joelho/patologia , Transporte Proteico
2.
Int J Mol Sci ; 22(6)2021 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-33802646

RESUMO

The aim of this study was to determine the effects of ß-hydroxy-ß-methylbutyrate (HMB) supplementation during pregnancy on postpartum bone tissue quality by assessing changes in trabecular and compact bone as well as in hyaline and epiphyseal cartilage. The experiment was carried out on adult 6-month-old female spiny mice (Acomys cahirinus) divided into three groups: pregnant control (PregCont), pregnant HMB-treated (supplemented with 0.02 g/kg b.w of HMB during the second trimester of pregnancy, PregHMB), and non-pregnant females (NonPreg). Cross-sectional area and cortical index of the femoral mid-shaft, stiffness, and Young modulus were significantly greater in the PregHMB group. Whole-bone mineral density was similar in all groups, and HMB supplementation increased trabecular number. Growth plate cartilage was the thinnest, while the articular cartilage was the thickest in the PregHMB group. HMB supplementation increased the content of proteoglycans in the articular cartilage and the percentage of immature collagen content in metaphyseal trabeculae and compact bone. In summary, dietary HMB supplementation during the second trimester of pregnancy intensifies bone metabolic processes and prevents bone loss during pregnancy.


Assuntos
Reabsorção Óssea/tratamento farmacológico , Reabsorção Óssea/prevenção & controle , Valeratos/uso terapêutico , Animais , Peso Corporal/efeitos dos fármacos , Reabsorção Óssea/diagnóstico por imagem , Osso Esponjoso/diagnóstico por imagem , Osso Esponjoso/efeitos dos fármacos , Osso Esponjoso/patologia , Cartilagem Articular/diagnóstico por imagem , Cartilagem Articular/efeitos dos fármacos , Cartilagem Articular/patologia , Colágeno/metabolismo , Epífises/efeitos dos fármacos , Epífises/patologia , Feminino , Fêmur/diagnóstico por imagem , Fêmur/efeitos dos fármacos , Fêmur/patologia , Murinae , Gravidez , Proteoglicanas/metabolismo , Valeratos/farmacologia , Microtomografia por Raio-X
3.
Int J Mol Sci ; 22(6)2021 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-33804203

RESUMO

Osteoarthritis (OA) is a common degenerative disease that results in joint inflammation as well as pain and stiffness. A previous study has reported that Cornus officinalis (CO) extract inhibits oxidant activities and oxidative stress in RAW 264.7 cells. In the present study, we isolated bioactive compound(s) by fractionating the CO extract to elucidate its antiosteoarthritic effects. A single bioactive component, morroniside, was identified as a potential candidate. The CO extract and morroniside exhibited antiosteoarthritic effects by downregulating factors associated with cartilage degradation, including cyclooxygenase-2 (Cox-2), matrix metalloproteinase 3 (Mmp-3), and matrix metalloproteinase 13 (Mmp-13), in interleukin-1 beta (IL-1ß)-induced chondrocytes. Furthermore, morroniside prevented prostaglandin E2 (PGE2) and collagenase secretion in IL-1ß-induced chondrocytes. In the destabilization of the medial meniscus (DMM)-induced mouse osteoarthritic model, morroniside administration attenuated cartilage destruction by decreasing expression of inflammatory mediators, such as Cox-2, Mmp3, and Mmp13, in the articular cartilage. Transverse microcomputed tomography analysis revealed that morroniside reduced DMM-induced sclerosis in the subchondral bone plate. These findings suggest that morroniside may be a potential protective bioactive compound against OA pathogenesis.


Assuntos
Cornus/química , Glicosídeos/farmacologia , Inflamação/tratamento farmacológico , Meniscos Tibiais/efeitos dos fármacos , Osteoartrite/tratamento farmacológico , Animais , Cartilagem Articular/efeitos dos fármacos , Condrócitos/efeitos dos fármacos , Ciclo-Oxigenase 2/genética , Dinoprostona/genética , Modelos Animais de Doenças , Regulação da Expressão Gênica/efeitos dos fármacos , Glicosídeos/química , Humanos , Interleucina-1beta/genética , Metaloproteinase 13 da Matriz/genética , Metaloproteinase 3 da Matriz/genética , Meniscos Tibiais/patologia , Meniscos Tibiais/cirurgia , Camundongos , Osteoartrite/genética , Osteoartrite/patologia , Osteoartrite/cirurgia , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Cultura Primária de Células , Células RAW 264.7 , Transdução de Sinais/efeitos dos fármacos
4.
Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi ; 35(4): 519-526, 2021 Apr 15.
Artigo em Chinês | MEDLINE | ID: mdl-33855840

RESUMO

Objective: To review the pathological effects of cellular senescence in the occurrence and development of osteoarthritis (OA) and potential therapeutic targets. Methods: The role of chondrocyte senescence, synovial cell senescence, mesenchymal stem cells senescence in OA, and the biological mechanism and progress of chondrocyte senescence were summarized by consulting relevant domestic and abroad literature. Results: The existing evidence has basically made clear that chondrocyte senescence, mesenchymal stem cells senescence, and cartilage repair abnormalities, and the occurrence and development of OA have a certain causal relationship, and the role of the senescence of synovial cells, especially synovial macrophages in OA is still unclear. Transcription factors and epigenetics are the main mechanisms that regulate the upstream pathways of cellular senescence. Signal communication between cells can promote the appearance of senescent phenotypes in healthy cells. Targeted elimination of senescent cells and promotion of mesenchymal stem cells rejuvenation can effectively delay the progress of OA. Conclusion: Cellular senescence is an important biological phenomenon and potential therapeutic target in the occurrence and development of OA. In-depth study of its biological mechanism is helpful to the early prevention and treatment of OA.


Assuntos
Cartilagem Articular , Células-Tronco Mesenquimais , Osteoartrite , Senescência Celular , Condrócitos , Humanos , Macrófagos , Osteoartrite/etiologia
5.
Int J Mol Sci ; 22(6)2021 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-33801144

RESUMO

We are conducting a clinical study of the use of allogeneic polydactyly-derived chondrocyte sheets (PD sheets) for the repair of articular cartilage damage caused by osteoarthritis. However, the transplantation of PD sheets requires highly invasive surgery. To establish a less invasive treatment, we are currently developing injectable fragments of PD sheets (PD sheets-mini). Polydactyly-derived chondrocytes were seeded in RepCell™ or conventional temperature-responsive inserts and cultured. Cell counts and viability, histology, enzyme-linked immunosorbent assay (ELISA), quantitative real-time polymerase chain reaction (qPCR), and flow cytometry were used to characterize PD sheets-mini and PD sheets collected from each culture. To examine the effects of injection on cell viability, PD sheets-mini were tested in four experimental conditions: non-injection control, 18 gauge (G) needle, 23G needle, and syringe only. PD sheets-mini produced similar amounts of humoral factors as PD sheets. No histological differences were observed between PD sheets and PD sheets-mini. Except for COL2A1, expression of cartilage-related genes did not differ between the two types of PD sheet. No significant differences were observed between injection conditions. PD sheets-mini have characteristics that resemble PD sheets. The cell viability of PD sheets-mini was not significantly affected by needle gauge size. Intra-articular injection may be a feasible, less invasive method to transplant PD sheets-mini.


Assuntos
Condrócitos/citologia , Polidactilia , Tecidos Suporte , Animais , Biomarcadores , Cartilagem Articular , Contagem de Células , Sobrevivência Celular , Condrócitos/metabolismo , Expressão Gênica , Humanos , Imuno-Histoquímica , Imunofenotipagem , Osteoartrite/terapia , Regeneração
6.
Int J Mol Sci ; 22(7)2021 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-33807323

RESUMO

A continuing challenge in cartilage tissue engineering for cartilage regeneration is the creation of a suitable synthetic microenvironment for chondrocytes and tissue regeneration. The aim of this study was to develop a highly tunable hybrid scaffold based on a silk fibroin matrix (SM) and a hyaluronic acid (HA) hydrogel. Human articular chondrocytes were embedded in a porous 3-dimensional SM, before infiltration with tyramine modified HA hydrogel. Scaffolds were cultured in chondropermissive medium with and without TGF-ß1. Cell viability and cell distribution were assessed using CellTiter-Blue assay and Live/Dead staining. Chondrogenic marker expression was detected using qPCR. Biosynthesis of matrix compounds was analyzed by dimethylmethylene blue assay and immuno-histology. Differences in biomaterial stiffness and stress relaxation were characterized using a one-step unconfined compression test. Cell morphology was investigated by scanning electron microscopy. Hybrid scaffold revealed superior chondro-inductive and biomechanical properties compared to sole SM. The presence of HA and TGF-ß1 increased chondrogenic marker gene expression and matrix deposition. Hybrid scaffolds offer cytocompatible and highly tunable properties as cell-carrier systems, as well as favorable biomechanical properties.


Assuntos
Cartilagem Articular/metabolismo , Fibroínas/farmacologia , Engenharia Tecidual/métodos , Idoso , Materiais Biocompatíveis/metabolismo , Cartilagem/citologia , Cartilagem/metabolismo , Cartilagem Articular/citologia , Sobrevivência Celular/fisiologia , Células Cultivadas , Condrócitos/metabolismo , Condrogênese , Fibroínas/metabolismo , Humanos , Ácido Hialurônico/farmacologia , Hidrogéis/metabolismo , Hidrogéis/farmacologia , Pessoa de Meia-Idade , Porosidade , Seda/metabolismo , Tecidos Suporte/química
7.
Int J Mol Sci ; 22(5)2021 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-33800860

RESUMO

In the knee joint, articular cartilage injury can often lead to osteoarthritis of the knee (OAK). Currently, no point-of-care treatment can completely address OAK symptoms and regenerate articular cartilage to restore original functions. While various cell-based therapies are being developed to address OAK, exosomes containing various components derived from their cells of origin have attracted attention as a cell-free alternative. The potential for exosomes as a novel point-of-care treatment for OAK has been studied extensively, especially in the context of intra-articular treatments. Specific exosomal microRNAs have been identified as possibly effective in treating cartilage defects. Additionally, exosomes have been studied as biomarkers through their differences in body fluid composition between joint disease patients and healthy subjects. Exosomes themselves can be utilized as a drug delivery system through their manipulation and encapsulation of specific contents to be delivered to specific cells. Through the combination of exosomes with tissue engineering, novel sustained release drug delivery systems are being developed. On the other hand, many of the functions and activities of exosomes are unknown and challenges remain for clinical applications. In this review, the possibilities of intra-articular treatments utilizing exosomes and the challenges in using exosomes in therapy are discussed.


Assuntos
Exossomos , MicroRNAs/uso terapêutico , Osteoartrite do Joelho/terapia , Sistemas Automatizados de Assistência Junto ao Leito , Animais , Autofagia , Biomarcadores , Cartilagem Articular/fisiologia , Condrócitos/metabolismo , Preparações de Ação Retardada , Modelos Animais de Doenças , Sistemas de Liberação de Medicamentos , Exossomos/química , Exossomos/ultraestrutura , Humanos , Injeções Intra-Articulares , Artropatias/diagnóstico , Artropatias/terapia , Macrófagos/fisiologia , MicroRNAs/administração & dosagem , Osteoartrite do Joelho/diagnóstico , Regeneração
8.
Orthopade ; 50(5): 356-365, 2021 May.
Artigo em Alemão | MEDLINE | ID: mdl-33844031

RESUMO

BACKGROUND: Commonly used cartilage repair procedures have been established for focal cartilage lesions; however, degenerative lesions with accompanying changes of other intraarticular structures are much more common in clinical practice. This stage, in which classic radiological signs of osteoarthritis are absent, is called early osteoarthritis and is characterized by impaired joint homeostasis with biomechanical and biochemical changes that can have a negative effect on regenerative cartilage therapy procedures. INDICATION: Cartilage repair procedures are indicated for symptomatic focal early osteoarthritis, defined as cartilage degeneration ICRS grades I or II around a focal cartilage defect ICRS grades III or IV. In more advanced osteoarthritis with significant narrowing of the joint space, cartilage repair procedures are generally contraindicated. THERAPY: The most studied cartilage repair procedure for early osteoarthritis is autologous chondrocyte implantation, which has shown acceptable results in case series, although higher failure rates are to be expected compared to focal, traumatic cartilage lesions. The use of bone marrow-stimulating techniques seems to be limited in early osteoarthritis and should only be used in cases of lesion < 2 cm2 and very little surrounding cartilage degeneration. Concomitant surgical procedures, especially unloading osteotomies, are very important.


Assuntos
Doenças das Cartilagens , Cartilagem Articular , Osteoartrite , Cartilagem Articular/diagnóstico por imagem , Cartilagem Articular/cirurgia , Condrócitos , Humanos , Articulação do Joelho , Osteoartrite/diagnóstico por imagem , Osteoartrite/cirurgia , Resultado do Tratamento
9.
Int J Mol Sci ; 22(7)2021 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-33808364

RESUMO

Osteoarthritis (OA) of the knee is a disease that significantly decreases the quality of life due to joint deformation and pain caused by degeneration of articular cartilage. Since the degeneration of cartilage is irreversible, intervention from an early stage and control throughout life is important for OA treatment. For the treatment of early OA, the development of a disease-modifying osteoarthritis drug (DMOAD) for intra-articular (IA) injection, which is attracting attention as a point-of-care therapy, is desired. In recent years, the molecular mechanisms involved in OA progression have been clarified while new types of drug development methods based on gene sequences have been established. In addition to conventional chemical compounds and protein therapeutics, the development of DMOAD from the new modalities such as gene therapy and oligonucleotide therapeutics is accelerating. In this review, we have summarized the current status and challenges of DMOAD for IA injection, especially for protein therapeutics, gene therapy, and oligonucleotide therapeutics.


Assuntos
Osteoartrite do Joelho/tratamento farmacológico , Osteoartrite/tratamento farmacológico , Cartilagem Articular/efeitos dos fármacos , Descoberta de Drogas/métodos , Reposicionamento de Medicamentos/métodos , Humanos , Injeções Intra-Articulares/métodos , Articulação do Joelho/efeitos dos fármacos , Dor/tratamento farmacológico
10.
BMC Musculoskelet Disord ; 22(1): 329, 2021 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-33812379

RESUMO

BACKGROUND: Animal model of Knee Osteoarthritis (OA) is the primary testing methodology for studies on pathogenic mechanisms and therapies of human OA disease. Recent major modeling methods are divided into artificially induced and spontaneous. However, these methods have some disadvantages of slow progression, high cost and no correlation with the pathogenesis of OA. METHODS: Our studies attempted to find a rapid, easy, and consistent with the natural pathological process of OA modeling method by intra-articular injection of stromal cell-derived factor 1 (SDF-1) in the rabbit knee. After induction we collected cartilage specimens from the medial femoral condyle to undergo macroscopic, histological, immunohistochemical, and biochemical evaluations. Meanwhile, compared with Hulth surgical method to evaluate its efficacy. RESULTS: Macroscopic observation and modified Mankin score of histological staining exhibited typical features of middle stage OA cartilage in SDF-1 injected groups. Immunohistochemically, the positive expression of interleukin-1 (IL-1) and tumor necrosis factor α(TNF-α) was earlier and higher in high dose SDF-1 group than the surgical group. The matrix metalloproteinases (MMPs) in synovial fluid and chondrocytes significantly increased, but type II collagen (COLII) and aggrecan (ACAN) protein expressions decreased in SDF-1 injected group following the extension of time and increase of SDF-1 concentration. CONCLUSIONS: Our data indicated intra-articular injection of SDF-1 (40µg/kg, three times for 12 weeks) can induce rabbit knee OA model successfully more rapidly and easily than traditional surgical modeling. The study provided a further option for the establishment of knee OA animal model.


Assuntos
Cartilagem Articular , Osteoartrite do Joelho , Animais , Cartilagem Articular/diagnóstico por imagem , Quimiocina CXCL12 , Condrócitos , Modelos Animais de Doenças , Injeções Intra-Articulares , Osteoartrite do Joelho/induzido quimicamente , Osteoartrite do Joelho/tratamento farmacológico , Coelhos
11.
BMC Musculoskelet Disord ; 22(1): 395, 2021 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-33910538

RESUMO

BACKGROUND: To observe the sequence of chondrocyte degeneration and matrix degradation in the superficial surface cartilage of the tibial plateau in guinea pigs with spontaneous knee osteoarthritis (OA). METHODS: Sixty guinea pigs were euthanized at the ages of 8 months (n = 20),10 months (n = 20) and 12 months (n = 20) respectively. The degree of degeneration of the tibial plateau cartilage was evaluated by Osteoarthritis Research Society International (OARSI) score. The levels of Aggrecan,CollagenX,MMP-13 and Caspase-3 in the chondrocytes were detected by immunohistochemistry (IHC). The serum concentration of CTX-II was measured and compared. Western blot analysis was used to detect the levels of Aggrecan,CollagenX,MMP-13 and Caspase-3 in the cartilage tissue. RESULTS: The OARSI scores both in 8-month-old group and 10-month-old group were lower than that in the 12-month-old group. The levels of Aggrecan in articular chondrocyte were higher both in 8-month-old group and 10-month-old group than that in 12-month-old group. The level of Collagen X increased with the age of guinea pigs. And the levels of MMP-13 and caspase-3 both in 10-month-old group and 12-month-old group were higher than those in 8-month-old group. The concentration of CTX-II in serum increased significantly in 12 months old group. CONCLUSION: The superficial chondrocytes of the tibial plateau first appeared to be hypertrophic and then apoptotic, and the matrix was further degraded when spontaneous knee osteoarthritis occurred in guinea pigs. Changes in the physiological state of chondrocytes are the initiating factors in the pathogenesis of knee OA.


Assuntos
Cartilagem Articular , Osteoartrite do Joelho , Agrecanas , Animais , Condrócitos , Cobaias , Tíbia
12.
J Surg Orthop Adv ; 30(1): 10-13, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33851907

RESUMO

While basic science research confirms the robust biological profile of juvenile chondrocytes, the clinical outcomes after particulated juvenile cartilage allograft transplantation are not well established. A retrospective analysis of active duty servicemembers undergoing surgical treatment with particulated juvenile articular cartilage allograft transplantation for chondral defects of the knee from two military treatment facilities was completed. Demographic variables, operative details, activity limitations, and medical discharges were obtained. A total of 29 patients with 36 treated chondral defects were isolated at an average follow-up of 16.2 months. The cohort was comprised of male service members in the Army with mean age of 33.1 years. Location of chondral lesion included the patellofemoral articulation (patella 39%, trochlea 31%, bipolar lesions 8%) and condyles (31%). Offloading or realignment osteotomy procedures were performed in 7 patients (23%). Of all patients, 14 servicemembers (48%) underwent knee-related medical discharge, and one patient underwent conversion to total knee arthroplasty. In this small patient cohort, particulated juvenile cartilage allograft transplantation for chondral defects of the knee did not reliably restore military servicemembers to full military function. At least one in two patients had persisting knee pain after chondral restoration procedure. (Journal of Surgical Orthopaedic Advances 30(1):010-013, 2021).


Assuntos
Cartilagem Articular , Adulto , Aloenxertos , Cartilagem Articular/cirurgia , Humanos , Articulação do Joelho/cirurgia , Masculino , Estudos Retrospectivos , Sobrevivência
13.
Int J Mol Sci ; 22(6)2021 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-33799588

RESUMO

We have been studying mesenchymal stem cells (MSCs) in synovial fluid and the intra-articular injection of synovial MSCs in osteoarthritis (OA) knees. Here, mainly based on our own findings, we overview the characteristics of endogenous MSCs in the synovial fluid of OA knees and their mode of action when injected exogenously into OA knees. Many MSCs similar to synovial MSCs were detected in the synovial fluid of human OA knees, and their number correlated with the radiological OA grade. Our suspended synovium culture model demonstrated the release of MSCs from the synovium through a medium into a non-contacting culture dish. In OA knees, endogenous MSCs possibly mobilize in a similar manner from the synovium through the synovial fluid and act protectively. However, the number of mobilized MSCs is limited; therefore, OA progresses in its natural course. Synovial MSC injections inhibited the progression of cartilage degeneration in a rat OA model. Injected synovial MSCs migrated into the synovium, maintained their MSC properties, and increased the gene expressions of TSG-6, PRG-4, and BMP-2. Exogenous synovial MSCs can promote anti-inflammation, lubrication, and cartilage matrix synthesis in OA knees. Based on our findings, we have initiated a human clinical study of synovial MSC injections in OA knees.


Assuntos
Condrogênese/genética , Transplante de Células-Tronco Mesenquimais/métodos , Células-Tronco Mesenquimais/fisiologia , Osteoartrite do Joelho/terapia , Líquido Sinovial/fisiologia , Animais , Proteína Morfogenética Óssea 2/genética , Proteína Morfogenética Óssea 2/metabolismo , Cartilagem Articular/metabolismo , Cartilagem Articular/patologia , Moléculas de Adesão Celular/genética , Moléculas de Adesão Celular/metabolismo , Movimento Celular , Proliferação de Células , Modelos Animais de Doenças , Regulação da Expressão Gênica , Humanos , Injeções Intra-Articulares , Células-Tronco Mesenquimais/citologia , Osteoartrite do Joelho/genética , Osteoartrite do Joelho/metabolismo , Osteoartrite do Joelho/patologia , Proteoglicanas/genética , Proteoglicanas/metabolismo , Ratos , Líquido Sinovial/citologia , Transplante Heterólogo , Resultado do Tratamento
14.
Int J Mol Sci ; 22(5)2021 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-33806315

RESUMO

Systemic injection of a nerve growth factor (NGF) antibody has been proven to have a significant relevance in relieving osteoarthritis (OA) pain, while its adverse effects remain a safety concern for patients. A local low-dose injection is thought to minimize adverse effects. In this study, OA was induced in an 8-week-old male Sprague-Dawley (SD) rat joint by monoiodoacetate (MIA) injection for 2 weeks, and the effect of weekly injections of low-dose (1, 10, and 100 µg) NGF antibody or saline (control) was evaluated. Behavioral tests were performed, and at the end of week 6, all rats were sacrificed and their knee joints were collected for macroscopic and histological evaluations. Results showed that 100 µg NGF antibody injection relieved pain in OA rats, as evidenced from improved weight-bearing performance but not allodynia. In contrast, no significant differences were observed in macroscopic and histological scores between rats from different groups, demonstrating that intra-articular treatment does not worsen OA progression. These results suggest that local administration yielded a low effective NGF antibody dose that may serve as an alternative approach to systemic injection for the treatment of patients with OA.


Assuntos
Anticorpos Monoclonais Humanizados/administração & dosagem , Artrite Experimental/terapia , Fator de Crescimento Neural/antagonistas & inibidores , Osteoartrite/terapia , Manejo da Dor/métodos , Animais , Artrite Experimental/patologia , Artrite Experimental/fisiopatologia , Cartilagem Articular/patologia , Relação Dose-Resposta Imunológica , Hiperalgesia/fisiopatologia , Hiperalgesia/terapia , Injeções Intra-Articulares , Ácido Iodoacético/toxicidade , Masculino , Fator de Crescimento Neural/imunologia , Osteoartrite/patologia , Osteoartrite/fisiopatologia , Ratos , Ratos Sprague-Dawley , Suporte de Carga/fisiologia
15.
Chin J Dent Res ; 24(1): 41-47, 2021 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-33890454

RESUMO

OBJECTIVE: To develop a novel chondrocyte condensation culture strategy recapitulating developmental condensation and construct self-organised cartilaginous tissue for cartilage regeneration. METHODS: Cell-condensation aggregate (CCA) was generated using the condensation culture method by sequential cell seeding. The chondrification capacities and biocompatibilities of CCA were assessed by comparison with the cell-scaffold complex (CSC), which was constructed by cell-scaffold coculture. Preclinical studies including implantation into nude mice subcutaneously and cartilage defect repair in rabbits were performed. RESULTS: CCA constructed by condensation culture exhibited a morphology of self-organised cartilaginous tissue. Meanwhile, the condensation culture inhibited or abolished expression of HOX genes including HOXC4 and HOXD8, which was partially consistent with developmental HOX gene expression patterns and associated with enhanced regeneration capacities. Compared with CSC, CCA showed a higher capacity for chondrification and regeneration of rabbit cartilage defects. CONCLUSION: The therapeutic assessments indicate that CCA is an efficient therapeutic tool for cartilage regeneration, providing a new strategy for tissue engineering by mimicking developmental events.


Assuntos
Cartilagem Articular , Animais , Condrócitos , Camundongos , Camundongos Nus , Coelhos , Regeneração , Engenharia Tecidual , Tecidos Suporte
16.
Medicine (Baltimore) ; 100(17): e25636, 2021 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-33907120

RESUMO

ABSTRACT: The cartilage endplate plays an important role in the stress distribution and nutrition metabolism of the intervertebral disc. The healing morphology of the endplate after spinal fracture and its effect on the intervertebral disc degeneration are still unclear.This was a retrospective study. Patients with traumatic single-level thoracolumbar fractures treated in our orthopedic trauma service center from June 2011 to May 2019 were included and the relevant data were collected from the medical records. Based on combined computed tomography and MRI images, the endplate injury status was determined (no endplate injury, unilateral and bilateral endplate injury). According to the location of the injury, endplate injury was further divided into endplate central injury and endplate peripheral injury. The degree of posttraumatic disc lesions and disc degeneration during follow-up were classified based on the Sander classification and the Pfirrmann classification, respectively. According to the T1 image of MRI at the final follow-up, the healing morphology of endplates was determined and classified. Univariate analyses and correlation analyses were performed to evaluate the within- and between-group differences.There were in total 51 patients included in this study. Cartilage endplate fracture was significantly closely related to the degree of degeneration of the intervertebral disc (P = .003). Injuries in different parts of the endplate have no significant effect on the intervertebral disc degeneration (P = .204). The healing morphology after endplate fracture significantly affected the degree of intervertebral disc degeneration (P = .001). The comparisons of groups showed that the effects of irregular healing and traumatic Schmorl nodes on disc degeneration were not statistically significant, but were significantly significant with increased curvature.These results suggest that the irregular healing and the traumatic Schmorl nodes are closely related to intervertebral disc degeneration. The presence and severity of the endplate injury can provide valuable information for individualized clinical decision-making processes.


Assuntos
Consolidação da Fratura , Degeneração do Disco Intervertebral/patologia , Parafusos Pediculares/efeitos adversos , Complicações Pós-Operatórias/patologia , Fraturas da Coluna Vertebral/patologia , Adulto , Cartilagem Articular/patologia , Feminino , Fixação Interna de Fraturas/efeitos adversos , Fixação Interna de Fraturas/instrumentação , Humanos , Disco Intervertebral/patologia , Degeneração do Disco Intervertebral/etiologia , Vértebras Lombares/lesões , Vértebras Lombares/cirurgia , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/etiologia , Estudos Retrospectivos , Fraturas da Coluna Vertebral/cirurgia , Vértebras Torácicas/lesões , Vértebras Torácicas/cirurgia , Tomografia Computadorizada por Raios X , Adulto Jovem
17.
Orthopade ; 50(5): 346-355, 2021 May.
Artigo em Alemão | MEDLINE | ID: mdl-33837442

RESUMO

BACKGROUND: Osteoarthritis (OA)-the progressive degeneration of synovial joints-is a worldwide problem that affects society, is associated with age and is the dominant reason for pain and immobility of the locomotor system. In the population, 70% of people over the age of 70 show some signs of OA. Overall, up to 25% of the total population is affected, due to the general aging of the population itself, and this is an increasing tendency. However, in people over the age of 40 the incidence of OA is already rising due to posttraumatic or secondary forms, like dysplasia, malalignment and other background factors. CLAIM: There is a high need for mobility and sports in all generations, so the demands on the joints are high, especially if early degenerative changes are already present. Orthopaedic physicians are challenged with the limited load capacity, pain and the progressive joint problems, on the one hand to get the patient back to full mobility, and, on the other, to prevent early joint replacement. Early diagnosis and preventive measurements, as well as conservative treatments-from medication to braces-are necessary to achieve symptom-free movement and joint preservation to avoid joint replacement.


Assuntos
Cartilagem Articular , Osteoartrite , Cartilagem , Tratamento Conservador , Humanos , Articulações , Aparelhos Ortopédicos , Osteoartrite/diagnóstico , Osteoartrite/terapia
18.
Am J Sports Med ; 49(5): 1305-1312, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33667144

RESUMO

BACKGROUND: Although the toxic effects of bupivacaine on chondrocyte monolayer culture have been well described, its cellular and mechanical effects on native and engineered articular cartilage remain unclear. For the repair of articular cartilage defects, fresh autologous and allogenic cartilage grafts are commonly used, and engineered cell-based therapies are emerging. The outcome of grafting therapies aimed at repairing damaged cartilage relies largely on maintaining proper viability and mechanical suitability of the donor tissues. PURPOSE: To investigate the in vitro effects of single bupivacaine exposure on the viability and mechanics of 2 cartilage graft types: native articular cartilage and engineered neocartilage. STUDY DESIGN: Controlled laboratory study. METHODS: Articular cartilage explants were harvested from the bovine stifle femoral condyles, and neocartilage constructs were engineered from bovine stifle chondrocytes using the self-assembling process, a scaffold-free approach to engineer cartilage tissue. Both explants and neocartilage were exposed to chondrogenic medium containing a clinically applicable bolus of 0.5%, 0.25%, or 0% (control) bupivacaine for 1 hour, followed by fresh medium wash and exchange. Cell viability and matrix content (collagen and glycosaminoglycan) were assessed at t = 24 hours after treatment, and compressive mechanical properties were assessed with creep indentation testing at t = 5 to 6 days after treatment. RESULTS: Single bupivacaine exposure was chondrotoxic in both explants and neocartilage, with 0.5% bupivacaine causing a significant decrease in chondrocyte viability compared with the control condition (55.0% ± 13.4% vs 71.9% ± 13.5%; P < .001). Bupivacaine had no significant effect on matrix content for either tissue type. There was significant weakening of the mechanical properties in the neocartilage when treated with 0.5% bupivacaine compared with control, with decreased aggregate modulus (415.8 ± 155.1 vs 660.3 ± 145.8 kPa; P = .003), decreased shear modulus (143.2 ± 14.0 vs 266.5 ± 89.2 kPa; P = .002), and increased permeability (14.7 ± 8.1 vs 6.6 ± 1.7 × 10-15 m4/Ns; P = .009). Bupivacaine exposure did not have a significant effect on the mechanical properties of native cartilage explants. CONCLUSION: Single bupivacaine exposure resulted in significant chondrotoxicity in native explants and neocartilage and significant weakening of mechanical properties of neocartilage. The presence of abundant extracellular matrix does not appear to confer any additional resistance to the toxic effects of bupivacaine. CLINICAL RELEVANCE: Clinicians should be judicious regarding the use of intra-articular bupivacaine in the setting of articular cartilage repair.


Assuntos
Bupivacaína , Cartilagem Articular , Animais , Bovinos , Condrócitos , Condrogênese , Articulação do Joelho , Engenharia Tecidual
19.
Ageing Res Rev ; 67: 101315, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33684550

RESUMO

Mechanical loading is essential for chondrocyte health. Chondrocytes can sense and respond to various extracellular mechanical signals through an integrated set of mechanisms. Recently, it has been found that mitochondria, acting as critical mechanotransducers, are at the intersection between extracellular mechanical signals and chondrocyte biology. Much attention has been focused on identifying how mechanical loading-induced mitochondrial dysfunction contributes to the pathogenesis of osteoarthritis. In contrast, little is known regarding the mechanisms underlying functional alterations in mitochondria induced by mechanical stimulation. In this review, we describe how chondrocytes perceive environmental mechanical signals. We discuss how mechanical load induces mitochondrial functional alterations and highlight the major unanswered questions in this field. We speculate that AMP-activated protein kinase (AMPK), a master regulator of energy homeostasis, may play an important role in coupling force transmission to mitochondrial health and intracellular biological responses.


Assuntos
Cartilagem Articular , Osteoartrite , Biologia , Cartilagem Articular/metabolismo , Condrócitos/metabolismo , Humanos , Mecanotransdução Celular , Mitocôndrias , Osteoartrite/etiologia , Osteoartrite/metabolismo
20.
Hua Xi Kou Qiang Yi Xue Za Zhi ; 39(1): 108-114, 2021 Feb 01.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-33723946

RESUMO

Cartilage stem cells (CSCs) are cells that self-proliferate, have surface antigen expression, and have multidirectional differentiation potential in the articular cartilage. CSCs, as an ideal source of stem cells, has a good application prospect in stem cell therapy. This article reviews the CSCs markers, cartilage differentiation signaling pathway, and clinical treatment of osteoarthritis.


Assuntos
Cartilagem Articular , Osteoartrite , Diferenciação Celular , Condrócitos , Humanos , Células-Tronco
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