Cartilage Breakdown Research Articles

BLOCKING ROR2 IMPROVES CARTILAGE INTEGRITY AND PROVIDES PAIN RELIEF IN OSTEOARTHRITIS, IN PART BY MODULATING YAP SIGNALLING

Purpose: Osteoarthritis (OA) is the leading cause of chronic disability worldwide, affecting 12% of the population, and yet we still do not have a disease-modifying treatment. Cartilage breakdown is the hallmark of OA, and patients suffer from pain and loss of joint function/independence, severely affecting quality of life. Therefore, there is a huge unmet clinical need. Receptor tyrosine kinase-like orphan receptor 2 (ROR2) is a non-canonical WNT receptor that regulates the planar cell polarity pathway, controlling limb outgrowth during development.

DEFINING THE EFFECTS OF LOAD AND SLIDING SPEED ON THE ABILITY OF CARTILAGE TO SUPPORT LOAD

Purpose: A key feature of osteoarthritis (OA) is the breakdown of articular cartilage. The function of cartilage depends on its ability to support high loads via pressurization of its interstitial fluid—known as “fluid load support” (FLS). FLS depends on the balance of fluid exudation, which occurs during static loading, and fluid rehydration, which occurs during dynamic loading (e.g., walking). Importantly, when exudation and rehydration are perfectly balanced, cartilage achieves dynamic equilibrium deformation (DED).

EXOSOMAL CX43 DRIVES OSTEOARTHRITIS PROGRESSION BY ENHANCING CELLULAR PLASTICITY

Purpose: The accumulation of senescent cells is a key characteristic of aging, leading to the progression of age-related pathologies such as osteoarthritis (OA). Previous data from our laboratory has demonstrated that high levels of the transmembrane protein connexin43 (Cx43) are associated with a senescent phenotype in chondrocytes from osteoarthritic cartilage. OA has been reclassified as a musculoskeletal disease characterized by the breakdown of the articular cartilage affecting the whole joint, subchondral bone, synovium, ligaments, tendons and muscles.

SILENCING INFLAMMATORY SIGNALS IN CHONDROCYTES BY CRISPR/CAS9 FOR TISSUE ENGINEERED CELL THERAPY IN OSTEOARTHRITIS

Purpose: Osteoarthritis (OA) is one of the most common degenerative joint diseases, with limited therapeutic options that mostly focus on pain reduction. Restoration of cartilage surface by cell therapies is not effective due to the highly inflamed environment in the osteoarthritic joint. In OA, soluble IL-1β, LPS and TNFα activate the NFKB pathway in chondrocytes, leading to subsequent expression of other pro-inflammatory cytokines and cartilage-degrading enzymes and ultimately degenerative cartilage breakdown.

P13K-AKT PATHWAY AND PERIOSTIN UPREGULATED AFTER ANTERIOR CRUCIATE LIGAMENT RECONSTRUCTION: POTENTIAL ROLE IN EARLY POSTTRAUMATIC CARTILAGE DEGRADATION?

Purpose: Currently the standard of care for anterior cruciate ligament (ACL) injury in the United States is reconstruction, and while surgery has been demonstrated to improve patient-reported outcomes and restore ligamentous stability, ACL reconstruction has not been found to be protective against posttraumatic osteoarthritis (PTOA). Previous studies have demonstrated that ACL injury triggers a series of inflammatory events that leads to a sustained increase in inflammatory cytokines and biomarkers of cartilage breakdown in synovial fluid, and this process is re-initiated after ACL reconstruction.

Changes in ankle and foot kinematic after fixed-bearing total ankle replacement

Ankle osteoarthritis is a chronic debilitating disease marked by cartilage breakdown, pain and significant biomechanical impairment of the entire lower limb. Total ankle replacement (TAR) has been encouraged during the last decade as it has the potential to maintain the existing pre-operative ankle range of motion and to protect the more distally located joints of the foot. Three-dimensional gait analysis using a multi-segment foot model can provide an objective analysis of TAR for the treatment of end-stage ankle osteoarthritis. Thirty-six patients suffering from post-traumatic end-stage ankle osteoarthritis were evaluated before and after TAR. A four-segment kinematic foot model was used to calculate intrinsic foot joint kinematics during gait. Spatio-temporal parameters were also assessed. Kinematic results were compared to a control group of asymptomatic subjects.Differences in waveform patterns were mainly limited to dorsi-/plantarflexion inter-segment angles. At loading response, the Shank-Calcaneus plantarflexion angles as well as the Calcaneus-Midfoot dorsiflexion angle increased slightly in post-operative condition. During propulsion, an increase in Hallux-Metatarsus dorsiflexion angle was observed. Pain improved after surgery as supported by increased spatio-temporal parameters. While multi-segment foot and ankle kinematics were improved, they remained impaired compared to control values. This study confirms that TAR maintains the residual pre-operative range of motion after surgery from midstance to propulsion. Furthermore, the results suggest that the kinematic behavior of the foot joints distal to the affected ankle joint also improves post-operatively. The outcome of this study further emphasizes the clinical relevance of multi-segment foot modeling when assessing the outcome of TAR.

Multibody Computer Model of the Entire Equine Forelimb Simulates Forces Causing Catastrophic Fractures of the Carpus during a Traditional Race.

Simple SummaryPalios are traditional horseraces held in the main square of few Italian cities. Due to peculiar features of such circuits, adapted to the square architecture and thus characterized by tight curves and unconventional footing surface, horses involved are at particular risk of accidents. Prevention of catastrophic musculoskeletal injuries is a significant issue and matter of debate during these events. In particular, the negotiation of the curves in the city circuits is a significative concern. An experiment was set up to build a model of entire forelimb at the point of failure in the context of a turn comparable to that in a Palio circuit. The model was informed by live data and the output compared to post-mortem findings obtained from a horse that sustained a catastrophic fracture of the carpus during this competition. The objective of this study is to determine the magnitude and distribution of internal forces generated across the carpus under which the catastrophic injury has occurred and describe related post-mortem findings.A catastrophic fracture of the radial carpal bone experienced by a racehorse during a Palio race was analyzed. Computational modelling of the carpal joint at the point of failure informed by live data was generated using a multibody code for dynamics simulation. The circuit design in a turn, the speed of the animal and the surface characteristics were considered in the model. A macroscopic examination of the cartilage, micro-CT and histology were performed on the radio-carpal joint of the limb that sustained the fracture. The model predicted the points of contact forces generated at the level of the radio-carpal joint where the fracture occurred. Articular surfaces of the distal radius, together with the proximal articular surface of small carpal bones, exhibited diffuse wear lines, erosions of the articular cartilage and subchondral bone exposure. Even though the data in this study originated from a single fracture and further work will be required to validate this approach, this study highlights the potential correlation between elevated impact forces generated at the level of contact surfaces of the carpal joint during a turn and cartilage breakdown in the absence of pre-existing pathology. Computer modelling resulted in a useful tool to inversely calculate internal forces generated during specific conditions that cannot be reproduced in-vivo because of ethical concerns.

Management of osteoarthritis: From drug molecules to nano/micromedicines.

With the change in lifestyle and aging of the population, osteoarthritis (OA) is emerging as a major medical burden globally. OA is a chronic inflammatory and degenerative disease initially manifesting with joint pain and eventually leading to permanent disability. To date, there are no drugs available for the definitive treatment of osteoarthritis and most therapies have been palliative in nature by alleviating symptoms rather than curing the disease. This coupled with the vague understanding of the early symptoms and methods of diagnosis so that the disease continues as a global problem and calls for concerted research efforts. A cascade of events regulates the onset and progression of osteoarthritis starting with the production of proinflammatory cytokines, including interleukin (IL)‐1β, IL‐6, tumor necrosis factor (TNF)‐α; catabolic enzymes, such as matrix metalloproteinases (MMPs)‐1, ‐3, and ‐13, culminating into cartilage breakdown, loss of lubrication, pain, and inability to load the joint. Although intra‐articular injections of small and macromolecules are often prescribed to alleviate symptoms, low residence times within the synovial cavity severely impair their efficacy. This review will briefly describe the factors dictating the onset and progression of the disease, present the current clinically approved methods for its treatment and diagnosis, and finally elaborate on the main challenges and opportunities for the application of nano/micromedicines in the treatment of osteoarthritis. Thus, future treatment regimens will benefit from simultaneous consideration of the mechanobiological, the inflammatory, and tissue degradation aspects of the disease.This article is categorized under:Nanotechnology Approaches to Biology > Nanoscale Systems in BiologyImplantable Materials and Surgical Technologies > Nanotechnology in Tissue Repair and Replacement

Sex, but not age and bone mass index positively impact on the development of osteochondral micro-defects and the accompanying cellular alterations during osteoarthritis progression.

BackgroundOsteoarthritis (ΟΑ) is characterized by cartilage breakdown and subchondral sclerosis. Micro‐fractures of the calcified tissues have been, also, detected, but their exact role has not been elucidated yet. This study was to examine the frequency of cracks during OA progression and to correlate them with the underlying cellular modifications and matrix metalloproteinase‐2 (MMP‐2) expression using histological/immunohistological methods.MethodsOverall, 20 patients and 3 controls (9 specimens per patient), aged 60–89 years, diagnosed with hip/knee OA were included. The development of cracks was examined in 138 sections, whereas the expression of MMP‐2 was examined in 69 additional sections.ResultsBased on Mankin score, three groups of OA severity were analyzed: Group I (mild) was constituted of sections with score 1–5 while Groups II (moderate) and III (severe) with score 6–7 and greater or equal to 8, respectively. Demographic characteristics did not reveal any association between the number of microdefects and age or body mass index (BMI). Cartilage micro‐cracks were increased during moderate and severe OA, while bone cracks were increased during mild and severe OA. In knee OA, cartilage cracks were not correlated with Mankin score, whereas in hip OA they appeared association with severity score. Bone cracks were positively correlated with matrix apoptotic osteocytes and osteoblastic cells, but not with osteoclasts. MMP‐2 immunostaining was increasing by OA severity in the osteochondral unit. Similarly, MMP‐2 was expressed on the microcracks’ wall mainly in Group III.ConclusionOur data displayed that bone cracks during primary OA stages, represent an early adaptative mechanism aiming to maintain cartilage integrity. Accumulation of bone defects and concomitant increase of apoptotic osteocytes activated an abnormal remodeling due to osteoblastic activity, in which MMP‐2 played a pivotal role, leading to subchondral sclerosis promoting further osteochondral deformities.

MANAGEMENT OF PHYSIOTHERAPY IN THE CASE OF OSTEOARTHRITIS GENU DEXTRA IN KRAKATAU MEDIKA HOSPITAL

Background: Osteoarthritis is also known as calcification of the joints. The main disorder of osteoarthritis is the breakdown of joint cartilage. Joint cartilage is a joint component that lines the ends of bones in joints, functions as a cushion and shock absorber when two bones collide when the joint is moved (1) Complaints of joint pain usually come and go and attack only a few joints. In
 
 
 the early stages, joint pain occurs after strenuous physical exercise and then disappears after rest. The complaint then progresses to joint stiffness when you wake up in the morning which disappears within 15-30 minutes and decreases after being moved (2). Objective: to determine the management of physiotherapy in the condition of genu dextra osteoarthritis at the Krakatau medika hospital. Method: quantitative research with cross sectional design. Measurement of research variables was only done once by observation. Results: The patient did the examination, there was motion pain in the right knee joint, limited right knee LGS, decreased muscle strength. Parameters used to evaluate pain using a vase, LGS with Goneo Meter, muscle strength with MMT. Patients have difficulty walking long distances, squatting to standing, for toileting, limited range of motion, decreased muscle strength. In this case the management given is MWD, Tens, exercise therapy (isometric exercise, Hold Relax). Conclusion: Giving these three modalities greatly affects the condition of knee osteoarthritis, which can help prevent and treat problems such as:1. reduce pain in the knee starting from tenderness and movement using the VDS scale, 2. increasing the range of motion of the joint with a goneometer, 3. increasing muscle strength with MMT, 4. increasing the patient's functional activity with the jette scale. Suggestion: Physiotherapists are advised to always try to improve knowledge so as to identify problems that can arise in patients and can perform appropriate physiotherapy interventions for successful therapy.

Liraglutide, a glucagon-like peptide 1 receptor agonist, exerts\xa0analgesic, anti-inflammatory and anti-degradative actions in osteoarthritis

Osteoarthritis (OA) is a common disabling disease worldwide, with no effective and safe disease-modifying drugs (DMOAD) in the market. However, studies suggest that drugs, such as liraglutide, which possess strong potential in decreasing low-grade systemic inflammation may be effective in treating OA. Therefore, the aim of this study was to examine the anti-inflammatory, analgesic, and anti-degradative effects in OA using in vitro and in vivo experiments. The results showed that intra-articular injection of liraglutide alleviated pain-related behavior in in vivo sodium monoiodoacetate OA mouse model, which was probably driven by the GLP-1R-mediated anti-inflammatory activity of liraglutide. Moreover, liraglutide treatment significantly decreased IL-6, PGE2 and nitric oxide secretion, and the expression of inflammatory genes in vitro in chondrocytes and macrophages in a dose-dependent manner. Additionally, liraglutide shifted polarized macrophage phenotype in vitro from the pro-inflammatory M1 phenotype to the M2 anti-inflammatory phenotype. Furthermore, liraglutide exerted anti-catabolic activity by significantly decreasing the activities of metalloproteinases and aggrecanases, a family of catabolic enzymes involved in cartilage breakdown in vitro. Overall, the findings of this study showed that liraglutide ameliorated OA-associated pain, possess anti-inflammatory and analgesic properties, and could constitute a novel therapeutic candidate for OA treatment.

Mitochondrial Transplantation Ameliorates the Development and Progression of Osteoarthritis.

Osteoarthritis (OA) is a common degenerative joint disease characterized by breakdown of joint cartilage. Mitochondrial dysfunction of the chondrocyte is a risk factor for OA progression. We examined the therapeutic potential of mitochondrial transplantation for OA. Mitochondria were injected into the knee joint of monosodium iodoacetate-induced OA rats. Chondrocytes from OA rats or patients with OA were cultured to examine mitochondrial function in cellular pathophysiology. Pain, cartilage destruction, and bone loss were improved in mitochondrial transplanted-OA rats. The transcript levels of IL-1β, TNF-α, matrix metallopeptidase 13, and MCP-1 in cartilage were markedly decreased by mitochondrial transplantation. Mitochondrial function, as indicated by membrane potential and oxygen consumption rate, in chondrocytes from OA rats was improved by mitochondrial transplantation. Likewise, the mitochondrial function of chondrocytes from OA patients was improved by coculture with mitochondria. Furthermore, inflammatory cell death was significantly decreased by coculture with mitochondria. Mitochondrial transplantation ameliorated OA progression, which is caused by mitochondrial dysfunction. These results suggest the therapeutic potential of mitochondrial transplantation for OA.

Low-Salt Diet Attenuates B-Cell- and Myeloid-Cell-Driven Experimental Arthritides by Affecting Innate as Well as Adaptive Immune Mechanisms.

A link between high sodium chloride (salt) intake and the development of autoimmune diseases was previously reported. These earlier studies demonstrated exacerbation of experimental autoimmune encephalomyelitis and colitis by excess salt intake associated with Th17- and macrophage-mediated mechanisms. Little is known about the impact of dietary salt intake on experimental arthritides. Here, we investigated if salt restriction can exert beneficial effects on collagen-induced arthritis (CIA) and K/BxN serum transfer-induced arthritis (STIA). CIA depends on both adaptive and innate immunity, while STIA predominantly mimics the innate immune cell-driven effector phase of arthritis. In both models, low salt (LS) diet significantly decreased arthritis severity compared to regular salt (RS) and high salt (HS) diet. We did not observe an aggravation of arthritis with HS diet compared to RS diet. Remarkably, in STIA, LS diet was as effective as IL-1 receptor blocking treatment. Complement-fixing anti-CII IgG2a antibodies are associated with inflammatory cell infiltration and cartilage destruction. LS diet reduced anti-CII IgG2a levels in CIA and decreased the anti-CII IgG2a/IgG1 ratios pointing toward a more Th2-like response. Significantly less inflammatory joint infiltrates and cartilage breakdown associated with reduced protein concentrations of IL-1 beta (CIA and STIA), IL-17 (CIA), and the monocyte chemoattractant protein-1 (MCP-1) (CIA) were detected in mice receiving LS diet compared to HS diet. However, we did not find a reduced IL-17A expression in CD4+ T cells upon salt restriction in CIA. Analysis of mRNA transcripts and immunoblots revealed a link between LS diet and inhibition of the p38 MAPK (mitogen-activated protein kinase)/NFAT5 (nuclear factor of activated T-cells 5) signaling axis in STIA. Further experiments indicated a decreased leukodiapedesis under LS conditions. In conclusion, dietary salt restriction ameliorates CIA and STIA, indicating a beneficial role of LS diet during both the immunization and effector phase of immune-mediated arthritides by predominantly modulating the humoral immunity and the activation status of myeloid lineage cells. Hence, salt restriction might represent a supportive dietary intervention not only to reduce cardiovascular risk, but also to improve human inflammatory joint diseases like rheumatoid arthritis.

HUBUNGAN AKTIVITAS FISIK PEKERJA TANI DENGAN KEJADIAN OSTEOARTHRITIS

Osteoarthritis (OA) is a chronic inflammatory disease of the joints due to cartilage breakdown. OA that is left untreated can cause pain, stiffness, swelling, and can lead to disability. Osteoarthritis can occur due to one of the factors which is physical activity that is too heavy. Physical activity and work as farmers and coolies can burden the joints that support the body, especially the knees and waist so that it is very risky to experience osteoarthritis. The purpose of this study was to determine the correlation between physical activity of farm workers that resulted in the incidence of osteoarthritis. This research is a quantitative research, the design of this research is descriptive correlation with cross sectional approach. The number of samples used as many as 113 respondents farm workers. Sample selection using non-probability sampling technique in the form of accidental sampling. Data were collected using the IPAQ questionnaire for measuring physical activity for the last 7 days, and the WOMAC questionnaire for assessing the incidence of osteoarthritis. The questionnaire was distributed directly and analyzed using the Spearman Rank test. The results of statistical tests obtained p-value 0,01 (p < 0,05) which indicates a correlation between physical activity of farm workers with the incidence of osteoarthritis.it is hope that village heads and health workers cam carry out health education activities, especially regarding osteoarthritis and how to prevent it so as not to increase the incidence of osteoarthritis in farmers.

Neutrophil elastase and its inhibitors-overlooked players in osteoarthritis.

Cartilage homeostasis is maintained by a delicate balance between anabolism and catabolism. In osteoarthritis, pathological biomechanics or injury triggers cartilage breakdown, nonresolving synovial inflammation, and bone changes, causing reduced joint mobility and incapacitating pain. Undoubtedly, the most important cartilage degrading collagenase during osteoarthritis, matrix metalloproteinase (MMP)-13, is activated by an unlikely player: neutrophil elastase. Although primarily associated with inflammatory arthritis, neutrophil elastase is present in the osteoarthritic joint, and through activating MMP-13, spurs a cascade of events leading not just to the aberrant destruction of the cartilage itself, but to the proteolysis of its own inhibitor, alpha-1-antitrypsin, as described in the new study by Wilkinson etal. Endowed with potent chondrogenic and cartilage-protective properties, the loss of alpha-1-antitrypsin from cartilage will have major consequences for osteoarthritis progression, and strategies to prevent its loss, or replace it, might provide an innovative treatment opportunity that should not be ignored. Comment on: https://doi.org/10.1111/febs.16127.

The Effect of High Nameable Features on Category Learning: An Eye-Tracking Study

Pathologies of skeletal muscle and connective tissue are usually closely related to the immune and nervous systems. Together, they involve cell differentiation pathways, and therefore they deserve several separate chapters. This chapter focuses on selected bone diseases. Osteoarthritis and osteoporosis are common bone diseases among the elderly. Osteoarthritis is the most common form of arthritis that causes joint pain, stiffness, and results in a breakdown of joint cartilage and underlying bone.

The potential remedy of melatonin on osteoarthritis.

Osteoarthritis (OA), the most common arthritis worldwide, is a degenerative joint disease characterized by progressive cartilage breakdown, subchondral remodeling, and synovial inflammation. Although conventional pharmaceutical therapies aimed to prevent further cartilage loss and joint dysfunction, there are no ideal strategies that target the pathogenesis of OA. Melatonin exhibits a variety of regulatory properties by binding to specific receptors and downstream molecules and exerts a myriad of receptor-independent actions via intracellular targets as a chondrocyte protector, an anti-inflammation modulator, and a free radical scavenger. Melatonin also modulates cartilage regeneration and degradation by directly/indirectly regulating the expression of main circadian clock genes, such as transcriptional activators [brain and muscle aryl hydrocarbon receptor nuclear translocator-like protein (Bmal) and circadian locomotor output cycles kaput (Clock)], transcriptional repressors [period circadian regulator (Per)1/2, cryptochrome (Cry)1/2, and Dec2], and nuclear hormone receptors [Rev-Erbs and retinoid acid-related orphan receptors (Rors)]. Owing to its effects on cartilage homeostasis, we propose a potential role for melatonin in the prevention and therapy of OA via the modulation of circadian clock genes, mitigation of chondrocyte apoptosis, anti-inflammatory activity, and scavenging of free radicals.

KARAKTERISTIK PASIEN OSTEOARTRITIS DI POLIKLINIK ORTOPEDI RS ROYAL PRIMA MEDAN

Osteoarthritis is a degenerative joint disease caused by the breakdown of joint cartilage, usually occurs in the spine, hips, knees, and ankles. This study aims to determine Overview Osteoarthritis Patient Characteristics Polyclinic Prima Royal Orthopaedic Hospital Medan. This study is a descriptive retrospective case study design with a sample of 100 samples were taken by purposive sampling is the most complete data. This study, obtained the highest age group 56-65 years of age by the amount of 41% by 41 people. Meanwhile, the lowest number in the 26-35 year age. This study, obtained the highest age group 56-65 years of age by the amount of 41% by 41 people. Meanwhile, the lowest number in the 26-35 year age that is 1% (1 people). Most gender is female 70% (70 people). Most jobs are housewives is 44% (44 people). Patients with a genetic history are 78% (78 people). Based on the largest weight factor is obese or overweight with 74% (74 people). The main complaint is joint pain as much as 100% (100 people). The most additional complaint is morning stiffness is 75% (75 people). Distribution of osteoarthritis patients based on the results of investigations that most anatomical changes occur joints by 77% (77 people). In Osteoarthritis patients are encouraged to maintain a healthy weight ideal and there should be an outreach to the community about Osteoarthritis society as much as possible in order to avoid factors originators.

Genetic Deletion of Interleukin-15 Is Not Associated with Major Structural Changes Following Experimental Post-Traumatic Knee Osteoarthritis in Rats

Post-traumatic osteoarthritis (PTOA) is a degenerative joint disease, leading to articular cartilage breakdown, osteophyte formation, and synovitis, caused by an initial joint trauma. Pro-inflammatory cytokines increase catabolic activity and may perpetuate inflammation following joint trauma. Interleukin-15 (IL-15), a pro-inflammatory cytokine, is increased in OA patients, although its roles in PTOA pathophysiology are not well characterized. Here, we utilized Il15 deficient rats to examine the role of IL-15 in PTOA pathogenesis in an injury-induced model. OA was surgically induced in Il15 deficient Holtzman Sprague-Dawley rats and control wild-type rats to compare PTOA progression. Semi-quantitative scoring of the articular cartilage, subchondral bone, osteophyte size, and synovium was performed by two blinded observers. There was no significant difference between Il15 deficient rats and wild-type rats following PTOA-induction across articular cartilage damage, subchondral bone damage, and osteophyte scoring. Similarly, synovitis scoring across six parameters found no significant difference between genetic variants. Overall, IL-15 does not appear to play a key role in the development of structural changes in this surgically-induced rat model of PTOA.

Matrix metalloproteinase-13 is fully activated by neutrophil elastase and inactivates its serpin inhibitor, alpha-1 antitrypsin: Implications for osteoarthritis.

Matrix metalloproteinase-13 (MMP-13) is a uniquely important collagenase that promotes the irreversible destruction of cartilage collagen in osteoarthritis (OA). Collagenase activation is a key control point for cartilage breakdown to occur, yet our understanding of the proteinases involved in this process is limited. Neutrophil elastase (NE) is a well-described proteoglycan-degrading enzyme which is historically associated with inflammatory arthritis, but more recent evidence suggests a potential role in OA. In this study, we investigated the effect of neutrophil elastase on OA cartilage collagen destruction and collagenase activation. Neutrophil elastase induced significant collagen destruction from human OA cartilage exvivo, in an MMP-dependent manner. Invitro, neutrophil elastase directly and robustly activated pro-MMP-13, and N-terminal sequencing identified cleavage close to the cysteine switch at 72 MKKPR, ultimately resulting in the fully active form with the neo-N terminus of 85 YNVFP. Mole-per-mole, activation was more potent than by MMP-3, a classical collagenase activator. Elastase was detectable in human OA synovial fluid and OA synovia which displayed histologically graded evidence of synovitis. Bioinformatic analyses demonstrated that, compared with other tissues, control cartilage exhibited remarkably high transcript levels of the major elastase inhibitor, (AAT) alpha-1 antitrypsin (gene name SERPINA1), but these were reduced in OA. AAT was located predominantly in superficial cartilage zones, and staining enhanced in regions of cartilage damage. Finally, active MMP-13 specifically inactivated AAT by removal of the serine proteinase cleavage/inhibition site. Taken together, this study identifies elastase as a novel activator of pro-MMP-13 that has relevance for cartilage collagen destruction in OA patients with synovitis.