L'arthrose (OA) est la maladie dégénérative la plus fréquente (ou) et la principale cause d'incapacité physique avec un coût socioéconomique important. Les manifestations cliniques de l'arthrose peuvent inclure des douleurs, des raideurs et des mouvements articulaires réduits. Pathologiquement, l'OA se caractérise par une dégénérescence progressive du cartilage articulaire, une augmentation de l'expression des médiateurs inflammatoires et cataboliques et le remodelage osseux sous-chondral. Il a été démontré que la protéine prostaglandine D2 (PGD2) est synthétisée par différents types cellulaires et possède des propriétés pro et anti-inflammatoires, selon le récepteur activé. Plusieurs stimuli pro-inflammatoires ont été discernés et étudiés, mais par contre, les voies anti-inflammatoires restent toujours un univers inexploré. Le récepteur DP1 de la PGD2, ainsi que l’enzyme de synthèse L-PGDS, jouent des rôles importants dans l'inflammation et le métabolisme du cartilage. Cependant, leurs rôles dans la pathogenèse de l'arthrose (OA) restent inconnus. Nous avons entrepris l’étude (de quoi) d’une part, pour explorer les rôles de la L- PGDS et de DP1 dans le développement d'OA, et d’autre part pour évaluer l'efficacité d'un agoniste sélectif de DP1 et d’un virus d'AAV2 / 5 codant pour L-PGDS dans le traitement de l'OA. En premier, nos travaux par histologie ont démontré que la dégradation du cartilage est plus prononcée chez les souris Knock-out L-PGDS et DP1, comparativement au souris sauvages Wild-Type (WT). Ensuite une augmentation de l’expression des médiateurs cataboliques (ADAMTS5 et MMP-13), chez les souris L-PGDS -/- et DP1 -/- par rapport au WT a été démontré. Après, la stimulation des explants de cartilage des souris L-PGDS -/- et de DP1 -/- avec l’IL-1a, ont montré une dégradation élevée en protéoglycanes. En outre ces souris ont développer aussi des modifications osseuses sous- chondral. Enfin, nos résultats suggèrent qu’à la suite d'injection intrapéritonéale de l’agoniste spécifique de DP1, le BW245C a atténué la gravité de la dégradation du cartilage induite par une déstabilisation du ménisque médiale (DMM) et des modifications osseuses chez les souris WT. Pareillement, l'injection intra-auriculaire d'AAV2 / 5 codant pour L- PGDS a atténué aussi la dégradation du cartilage induite par DMM et l'expression de ADAMTS-5 et MMP-13 chez des souris L-PGDS -/-. En conclusion, l’ensemble de nos résultats suggèrentque le récepteur DP1 et l’enzyme L-PGDS au niveau du cartilage articulaire arthrosique joue un rôle très important. . Elle pourrait constituer une voie thérapeutique potentielle dans le traitement de l’OA et aussi dans le traitement d’autres pathologies musculo-squelettiques. / Osteoarthritis (OA) is the most common degenerative disease (or) and the leading cause of physical disability with significant socioeconomic costs. Clinical manifestations of osteoarthritis can include pain, stiffness, and reduced joint movement. Pathologically, OA is characterized by progressive degeneration of articular cartilage, increased expression of inflammatory and catabolic mediators, and subchondral bone remodeling. It has been shown that prostaglandin D2 protein (PGD2) is synthesized by different cell types and has pro and anti-inflammatory properties, depending on the activated receptor. Several pro-inflammatory stimuli have been discerned and studied, but the anti- inflammatory pathways remain an unexplored universe. The DP1 receptor of PGD2, as well as the synthetic enzyme L-PGDS, play important roles in inflammation and cartilage metabolism. However, their roles in the pathogenesis of osteoarthritis (OA) remain unknown. We undertook the study (of what) on the one hand, to explore the roles of L-PGDS and DP1 in the development of OA, and on the other hand to evaluate the efficacy of a selective agonist DP1 and an AAV2 / 5 virus encoding L-PGDS in the treatment of OA. First, our histology work demonstrated that cartilage degradation is more pronounced in L- PGDS Knock-out and DP1 mice compared to Wild-Type (WT) wild-type mice. Then an increase in the expression of catabolic mediators (ADAMTS5 and MMP-13), in L-PGDS - / - mice and DP1 - / - compared to WT was demonstrated. Subsequently, stimulation of cartilage explants with IL-α from L-PGDS - / - and DP1 - / - mice showed high degradation in proteoglycans. In addition, these mice also develop subchondral bone changes. Finally, our results suggest that following intraperitoneal injection of the DP1-specific agonist, BW245C attenuated the severity of cartilage degradation induced by medial meniscus destabilization (DMM) and bone changes in mice. WT. Similarly, the intra-atrial injection of AAV2 / 5 encoding L-PGDS also attenuated DMM-induced cartilage degradation and the expression of ADAMTS-5 and MMP-13 in L-PGDS - / - mice. In conclusion, all our results suggest that the recepteur DP1 and the L-PGDS enzyme in osteorthritis cartilage plays a very important role. It may be a potential therapeutic avenue in the treatment of OA and also in the treatment of other musculoskeletal conditions.

This article provides a brief review of the pathophysiology of osteoarthritis and the ontogeny of chondrocytes and details how physical exercise improves the health of osteoarthritic joints and enhances the potential of autologous chondrocyte implants, matrix-induced autologous chondrocyte implants, and mesenchymal stem cell implants for the successful treatment of damaged articular cartilage and subchondral bone. In response to exercise, articular chondrocytes increase their production of glycosaminoglycans, bone morphogenic proteins, and anti-inflammatory cytokines and decrease their production of proinflammatory cytokines and matrix-degrading metalloproteinases. These changes are associated with improvements in cartilage organization and reductions in cartilage degeneration. Studies in humans indicate that exercise enhances joint recruitment of bone marrow-derived mesenchymal stem cells and upregulates their expression of osteogenic and chondrogenic genes, osteogenic microRNAs, and osteogenic growth factors. Rodent experiments demonstrate that exercise enhances the osteogenic potential of bone marrow-derived mesenchymal stem cells while diminishing their adipogenic potential, and that exercise done after stem cell implantation may benefit stem cell transplant viability. Physical exercise also exerts a beneficial effect on the skeletal system by decreasing immune cell production of osteoclastogenic cytokines interleukin-1β, tumor necrosis factor-α, and interferon-γ, while increasing their production of antiosteoclastogenic cytokines interleukin-10 and transforming growth factor-β. In conclusion, physical exercise done both by bone marrow-derived mesenchymal stem cell donors and recipients and by autologous chondrocyte donor recipients may improve the outcome of osteochondral regeneration therapy and improve skeletal health by downregulating osteoclastogenic cytokine production and upregulating antiosteoclastogenic cytokine production by circulating immune cells.

Osteoarthritis is a degenerative joint disease which affects the entire joint; however, one of its hallmarks is the progressive degeneration of the articular cartilage layer. Patients suffering from osteoarthritis exhibit chronic pain, stiffness, and a decreased range of motion, greatly affecting their quality of life. No drugs have been approved to stop the progression of osteoarthritis and focus solely on the management of symptoms. This is partly due to the challenges in delivering drugs to afflicted joints, and specifically to cartilage due to its lack of vasculature. While intra-articular injection holds promise for the local administration of drugs, small molecules are rapidly cleared from the synovial fluid. As a result, there is a need to develop effective drug delivery strategies to improve residence times in the joint to elicit a sustained therapeutic effect. Previous studies identified polyphosphate as a pro-anabolic molecule, promoting glycosaminoglycan and collagen accumulation in cartilage constructs. Therefore, polyphosphate may be a therapeutic of interest to address the degeneration of articular cartilage in patients suffering from osteoarthritis. In this study, calcium-polyphosphate and strontium-polyphosphate particles were synthesized and characterized as a potential drug carrier into articular cartilage. Physicochemical characterization revealed that the particles exhibit a spherical morphology, have a negative zeta potential, and are nanoscale in size. Biological characterization in chondrocytes confirmed cellular uptake of the particles and demonstrated a size and concentration-dependent cytotoxicity at high concentrations. Furthermore, treatment of chondrocytes with these particles resulted in a reduction in metabolic activity and cell proliferation, confirming biological effects. Preliminary studies using cartilage explants suggest that the particles can penetrate and be retained in cartilage tissue. Therefore, from the results obtained within this study, the polyphosphate-based particles may be a potential drug delivery strategy for delivery into articular cartilage.

No description available.

Osteoarthritis the quality and span of life in horses. Previous studies focused on nasal cartilage as a possible source for autologous chondrocyte implantation (ACI) in cartilage defects in humans. “HOX gene-negative” nasal chondrocytes adapted articular HOX patterns after implantation into caprine joint defects and produced cartilage matrix proteins. We compared the HOX gene profile of equine chondrocytes of nasal septum, anterior and posterior fetlock to identify nasal cartilage as a potential source for ACI in horses. Cartilage was harvested from seven horses after death and derived chondrocytes were cultured in a monolayer to fourth subcultivation. HOX A3, D1, D8 and chondrocyte markers COL2 and SOX9 were analyzed with qPCR in chondrocytes of three different locations obtained during passage 0 and passage 2. HOX gene expression showed no significant differences between the locations but varied significantly between the horses. HOX genes and SOX9 remained stable during culturing. Cultured nasal chondrocytes may be a target for future research in cell-based regenerative therapies in equine osteoarthritis. The involvement of HOX genes in the high regenerative and adaptive potential of nasal chondrocytes observed in previous studies could not be confirmed.

No description available.

No description available.

Yes / Articular cartilage, a connective tissue, contains chondrocytes and glycosaminoglycans (GAGs) which aid in water retention, providing the tissue with its magnificent ability to prevent friction, withstand loads and absorb compressive shocks however, cartilage, does not have the ability to regenerate and repair. Osteoarthritis (OA) is a progressive degenerative disease, which includes reduction of cartilage thickness between two bones in a joint, causing painful bone-to-bone contact. OA affects over 8 million people in the UK alone. , and as the primary causes are unknown, available treatments including surgical and non-surgical techniques which only reduce the symptoms created by the disorder instead of providing a cure. This project focused on utilizing TGF-β1, a cytokine found in elevated amounts in healthy cartilage when compared to degraded cartilage, in order to observe the effects of the growth factor on both healthy and osteoarthritic chondrocytes. The healthy and the osteoarthritic chondrocytes were cultured in two different media (DMEM with and without TGF- β1) before utilizing the SpectraMax M2/M2e plate reader to observe and analyze the effect of TGF-β1 on water retention properties of cells. This has been achieved by quantifying the GAG content using DMMB dye. Results showed that although TGF-β1 did displayed an increase in glycosaminoglycan synthesis, the statistical increase was not vast enough for the alternative hypothesis to be accepted; further experimentation with TGF-β1, alongside other cytokines within the growth factor family is needed to perceive the true influence of the growth factor on un cured degenerative diseases. It was concluded that both the healthy and osteoarthritic cells treated with TGF-β1 absorbed considerably more DMMB in comparison to the cells, suggesting that TGF-β1 indeed works to aid in water retention. TGF-β1 is a key factor to be exploited when constructing treatments for osteoarthritis

In the field of regenerative medicine, regeneration of cartilage defects (caused either by injury or age-related degeneration) has become a widely discussed topic. Nanofibrous scaffolds provide a suitable environment for cell adhesion, proliferation, differentiation, and also for the local involvement of bioactive substances. Nanofibrous scaffolds mimic the extracellular matrix (ECM) of hyaline cartilage. These scaffolds are seeded with autologous chondrocytes. After having been isolated from the patient, the cells must be cultivated in vitro in order to obtain a sufficient amount of chondrocytes. Scaffolds with cultivated chondrocytes are later implanted back into the pacient. Chondrocytes, however, when grown on a 2D tissue culture plastic rapidly de-differentiate and thus lose the ability to synthesize ECM molecules. The aim of the work was modulation of chondrogenic differentiation medium through finding the ideal concentration of chondrogenic supplements, composed of L-ascorbate-2-phosphate (A2P) and dexamethasone (DEX), in the culture of primary chondrocytes seeded on a nanofibrous polycaprolactone (PCL) scaffold. The effect of different concentrations of the chondrogenic supplements on chondrocyte adhesion to the scaffold and their proliferation and differentiation was studied. The influence...

Les fibrocartilages sont des tissus repartis largement dans l'organisme dont la structure histologique est étroitement liée à la fonction. Ils jouent un role fondamental dans la transmission des forces de compression ou de traction et sont un composant majeur de l' appareil musculo‐squelettique. Parmi les différents fibrocartilages se dégage l'enthèse qui vient attacher les tendons autour des articulations et dont le vieillissement aboutit à un arrachement des tendons. Afin d'étudier les possibilités thérapeutiques, nous avons developpé chez le petit animal, un modèle de lésion de l'enthèse qui se veut proche du vieillissement, afin de recréer un modèle translationnel le plus proche possible de la réalité clinique, ce modèle nous permettant d'évaluer le taux global de cicatrisation. Le modèle que nous avons développé nous a permis d'obtenir un taux de cicatrisation, après réparation chirurgicale d'une lésion de l'enthèse du tendon de rat, un taux de cicatrisation proche de celui obtenu en pratique clinique. En injectant, lors des réparations chirurgicales, des chondrocytes dans un groupe, et des cellules souches mésenchymateuses de la moelle osseuse dans l'autre nous avons montré une différence statistiquement significative en terme de taux global de cicatrisation, de résistance à l'arrachement, et de regénération histologique de l'enthèse à 45 jours