The contribution of the synovium, synovial derived inflammatory cytokines and neuropeptides to the pathogenesis of osteoarthritis (original) (raw)
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Le Centre pour la Communication Scientifique Directe - HAL - Diderot, 2000
Early detection of osteoarthritis in horses represents a challenge for equine practitioners. Several biological markers have been implicated in the pathological processes involved in articular cartilage destruction. To further document cartilage matrix proteases production, synovial fluid was collected from 14 horses (90 joints) before they were subjected to euthanasia. Growth macroscopic examination of the joints gave information on cartilage alterations. Samples were analyzed for matrix metalloproteinase (MMPs) activities by gelatin zymography and tumor necrosis factor alpha (TNF-α) cytotoxicity using L929 cells. Significant increase of MMP-9 monomer and dimer were found in synovial fluids of joints with severe cartilage alterations. On the contrary, the activity of TNF-α was not correlated to the degree of joint damage. The levels of MMP-9 monomer and dimer in the synovial fluid could reflect cartilage alteration in arthritis in the horse. horse / osteoarthritis / synovial fluid / metalloproteinase / tumor necrosis factor alpha Résumé-Activité des métalloprotéinases et du tumor necrosis factor-alpha dans le liquide synovial de chevaux : corrélation avec les altérations du cartilage articulaire. Le dépistage précoce des arthropathies reste un défi pour le vétérinaire équin. Certains marqueurs biologiques présents dans le liquide synovial pourraient être des indicateurs précoces de l'ostéoarthrose. C'est pourquoi, le liquide synovial de 90 articulations de 14 chevaux devant être euthanasiés a été recueilli. La dissection des articulations prélevées a ensuite permis de visualiser les surfaces articulaires. Pour chaque échantillon, l'activité des métalloprotéinases (MMPs) a été évaluée par zymographie et la cytotoxicité du tumor necrosis factor alpha (TNF-α) a été mesurée sur culture cellulaire. La corrélation des
American journal of translational research, 2021
The roles that cytokines and matrix metalloproteinases play in the onset and progression of posttraumatic osteoarthritis (PTOA) remain a topic of debate. The study objective was to evaluate the concentrations of these inflammatory mediators during the development of mild to moderate PTOA in the porcine anterior cruciate ligament (ACL) surgical model. We hypothesized that there would be more animals with detectable mediators in the pigs that develop moderate PTOA (those receiving ACL reconstruction or untreated ACL transection) compared to those that develop mild PTOA (those receiving scaffold-enhanced ACL repair). 36 Yucatan minipigs underwent ACL transection and were randomized to: 1) no further treatment, 2) ACL reconstruction, or 3) scaffold-enhanced ACL repair. Synovial fluid samples were obtained pre-operatively, and at 1, 4, 12, 26 and 52 weeks post-operatively. The concentrations of inflammatory mediator in the synovial fluid samples were evaluated via multiplex assay. Macros...
Journal of Equine Veterinary Science, 2015
The aim of this study is to evaluate the effect of pamidronate on the clinical score and the secretory profile of inflammatory biomarkers (IL-6, TNFα, MMP-2 and MMP-9) in the synovial fluid in clinically healthy horses and in horses with joint disease. Healthy horses and horses with joint symptoms were examined and subjected to a standardised clinical evaluation of the locomotor system. The clinical condition was evaluated by a global score. MMP-2 and MMP-9 were measured by gel zymography. The concentration of cytokines (IL-6 and TNF-α) in synovial fluid was determined by ELISA. Pamidronate treatment significantly improved the clinical condition of horses with osteoarthritis (OA). Values of IL-6 (pg/ml) were similar (ns) in the healthy control group (102.2±26.94) and at day 3 of treated group (TD3) (113.9±18.33). TNF-α level, at day 3 of treatment, was significantly lower in treated groups than in untreated osteoarthritis (UOA). TD group registered a fast increase in MMP-9 activity but till day 21 and 60 it was not detectable. No significant differences were found in the MMP-2
American Journal of Veterinary Research, 2001
Objectives—To determine concentrations of matrix metalloproteinase (MMP)-2 and -9 in synovial fluid; and mRNA expression of MMP-1, -13, and -3; interleukin[ IL]-1α and β; and tumor necrosis factor(TNF)-α in synovial membrane and articular cartilage from horses with naturally occurring joint disease. Sample Population—Synovial fluid (n = 76), synovial membrane (59), and articular cartilage (45) from 5 clinically normal horses and 55 horses with joint disease categorized as traumatic (acute [AT] or chronic [CT]), osteochondritis dissecans (OCD), or septic (S). Procedure—Synovial fluid gelatinase concentrations were analyzed, using zymography. Synovial membrane and articular cartilage mRNA expression for MMP-1, -3, and -13, IL-1α and β, TNF-α, type-II collagen, and aggrecan were analyzed, using quantitative reverse transcriptase-polymerase chain reaction. Results—Synovial fluid pro-MMP-2 concentration was significantly higher in diseased joints than normal joints. Septic joints had sig...
Conditioned media from human osteoarthritic synovium induces inflammation in a synoviocyte cell line
Connective tissue research, 2018
Osteoarthritis (OA) is a whole joint pathology involving cartilage, synovial membrane, meniscus, subchondral bone and infrapatellar fat pad (IFP). Synovitis has been widely documented in OA suggesting its important role in pathogenesis. The aim of this study was to investigate the role of different joint tissues in promoting synovitis. Conditioned media (CM) from cartilage, synovial membrane, meniscus and IFP, were generated from tissues of five patients undergoing total knee replacement and used to stimulate a human fibroblast-like synoviocytes cell line (K4IM). Cytokines, chemokines and metalloproteases release was analyzed in all CM by Bio-Plex Assay and sulfated glycosaminoglycan (GAG) content by dimethylmethylene blue assay. Gene expression of several markers was evaluated by Real-Time PCR in K4IM cells stimulated with the CM obtained from joint tissues. CM from all tissues produced high levels of IL-6, IL-8, and CCL2. CCL21, MMP-3 and -13 levels were detected in all CM except ...
2013
Objective: Evidence is accumulating that synovial tissue plays an active role in osteoarthritis (OA), however, exact understanding of its contribution is lacking. In order to further elucidate its role in the OA process, we aimed to identify the secretion pattern of soluble mediators by synovial tissue and to assess its ability to initiate cartilage degeneration. Methods: Synovial tissue explants (STEs) obtained from donors without history of OA (n = 8) or from end stage OA patients (n = 16) were cultured alone or together with bovine cartilage explants in the absence or presence of IL-1a. The secretion of 48 soluble mediators was measured and the effect on glycosaminoglycan (GAG) release and matrix metalloproteinase (MMP) activity was determined. Results: Normal and OA STEs secreted comparable levels of almost all measured soluble mediators. However, in the presence of IL-1a these mediators were less secreted by OA than by normal STEs of which 15 differed significantly (p,0.01). No effect of normal or OA STEs on GAG release from the cartilage explants was observed, and no differences in MMP activity between OA and normal STEs were detected. Conclusions: Unexpectedly, a comparable secretion profile of soluble mediators was found for OA and normal STEs while the reduced responsiveness of OA STEs to an inflammatory trigger indicates a different state of this tissue in OA patients. The effects could be the result of prolonged exposure to an inflammatory environment in OA development. Further understanding of the pro-inflammatory and inflammation resolving mechanisms during disease progression in synovial tissue may provide valuable targets for therapy in the future.
Synovial inflammation in osteoarthritis progression
Nature Reviews Rheumatology, 2022
Osteoarthritis (OA) is a progressive degenerative disease resulting in joint deterioration. Synovial inflammation is present in the OA joint and has been associated with radiographic and pain progression. Several OA risk factors, including ageing, obesity, trauma and mechanical loading, play a role in OA pathogenesis, likely by modifying synovial biology. In addition, other factors, such as mitochondrial dysfunction, damage-associated molecular patterns, cytokines, metabolites and crystals in the synovium, activate synovial cells and mediate synovial inflammation. An understanding of the activated pathways that are involved in OA-related synovial inflammation could form the basis for the stratification of patients and the development of novel therapeutics. This Review focuses on the biology of the OA synovium, how the cells residing in or recruited to the synovium interact with each other, how they become activated, how they contribute to OA progression and their interplay with other joint structures.
Annals of the Rheumatic Diseases, 1998
Objective-To investigate the influence of age, osteoarthritis (OA), and osteochondrosis (OC) on the matrix metalloproteinase (MMP) activity in the synovial fluid (SF) of equine joints. Methods-SF was collected from normal and osteoarthritic metacarpophalangeal joints (normal: 14 adult, 28 juvenile; OA: 22 adult). And from normal and osteochondrotic tarsocrural joints (5 months: 11 normal, 8 OC; 11 months: 7 normal, 6 OC). Subsequently, overall MMP activity was measured. Results-The level of active MMPs was almost twofold higher in SF from juvenile horses (age up to 11 months) than in SF from mature animals (4-30 years; p<0.001). In juvenile horses MMP activity was higher in 5 month old foals than in 11 month old foals (p<0.01). In adult horses MMP activity was independent of age. In OA joints the activity was nearly twice as high as in normal joints (p<0.001). In OC joints MMP activity was not significantly diVerent from normal, age matched, control joints. Conclusions-MMP activity in SF from normal adult joints is not related to age. In juvenile joints MMP activity is significantly higher than activity in joints from adult animals. It is hypothesised that the gradual decrease in MMP activity with increasing age reflects the declining metabolic activity resulting from ceasing growth and the accompanying decrease in cartilage remodelling. The increased MMP activity in osteoarthritic joints most likely reflects matrix destruction. In osteochondrosis MMP mediated matrix degradation appears not to be diVerent from normal joints.
Changes in Synovial Fluid Biomarkers after Experimental Equine Osteoarthritis
Journal of veterinary research, 2017
The study aimed to clarify the changes in the concentration of inflammatory mediators, proteases, and cartilage degradation biomarkers in the synovial fluid of joints in an equine osteoarthritis model. Osteoarthritis was induced in eight Mongolian horses by a sterile intra-articular injection of amphotericin B, which was injected into the left carpal joint in a dose of 2 mL (25 mg/mL). The control group comprised five horses which were injected with an equal dose of sterile physiological saline into the left carpal joint. Synovial fluid was obtained at baseline and every week after injection. Test methods were based on ELISA. In the course of the osteoarthritis, the concentration of biomarkers in joint synovial fluid showed an increasing trend. IL-1, IL-6, MMP-9, MMP-13, ADAMTS-5, CS846, GAG, HA, CTX-II, and COMP concentrations sharply increased before the onset of significant symptoms of lameness, whereas TNF-α, MMP-2, and MMP-3 concentrations rose sharply after the occurrence of s...
Osteoarthritis and Cartilage, 2015
Objective: The anti-inflammatory and anti-catabolic effects of neonatal Mesenchymal Stromal Cell (MSC) were investigated in a xenogeneic model of mild osteoarthritis (OA). The paracrine properties of MSC on synoviocytes were further investigated in vitro. Study design: OA was induced by medial meniscal release (MMR) in 30 rabbit knees. A single early (day 3) or delayed (day 15) intra-articular (IA) injection of MSC isolated from equine Umbilical Cord Wharton's jelly (UC-MSC) was performed. Rabbits were euthanized on days 15 or 56. OA grading was performed and gene expression of inflammatory cytokines and metalloproteinases was measured in synovial tissue. Paracrine effects of UC-MSC were investigated using UC-conditioned vs control medium on rabbit primary synoviocytes stimulated with interleukin 1 beta in vitro. Results: No adverse local or systemic responses were observed clinically after xenogeneic UC-MSC injection. At study end point, cartilage fibrillation was lower in early treatment than in delayed treatment group. Cellular infiltrate was observed in the synovium of both UC-MSC groups. OA synovium exhibited a reduced expression of metalloproteinases-1, -3, -13 in the early cell-treated group at d56. In vitro, UC-conditioned medium exerted anti-inflammatory and anti-catabolic effects on synoviocytes exposed to pro-inflammatory stimulus. Conclusions: Early IA injection of equine UC-MSC was effective in preventing OA signs in rabbit knees following MMR. UC-MSC target the synovium and modulate the gene expression pattern of synoviocytes to promote an anti-catabolic environment. This confirms the synovium is a major target and mediator of MSC therapy, modulating the expression of matrix-degrading enzymes. Osteoarthritis and Cartilage xxx (2014) 1e12 Please cite this article in press as: Saulnier N, et al., Intra-articular administration of xenogeneic neonatal Mesenchymal Stromal Cells early after meniscal injury down-regulates metalloproteinase gene expression in synovium and prevents cartilage degradation in a rabbit model of osteoarthritis, Osteoarthritis and Cartilage (2014), http://dx.