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Background/Objectives: Erosive hand osteoarthritis (EHOA) is an aggressive form of hand osteoarthritis (OA) and a severely disabling condition. Patients affected by OA frequently lament symptoms suggestive of neuropathic pain (NP). The aim of our study was to ascertain the presence and severity of NP in patients with EHOA and correlate its presence with EHOA clinical characteristics. Methods: In this retrospective study, we included all consecutive EHOA patients with NP symptoms who underwent upper limb electroneurography (ENoG) and nerve ultrasound. The presence of NP was screened using the ID pain neuropathic pain-screening questionnaire (ID-Pain). In addition, the following NP questionnaires were also used: Douleur Neuropathique en 4 Questions (DN4), PainDETECT, and Neuropathic Pain Symptom Inventory (NPSI). Moreover, patients completed the Australian/Canadian Osteoarthritis Hand Index (AUSCAN) and Dreiser's algofunctional finger index questionnaires assessing EHOA disease activity. The following clinical and laboratory data were collected: age, sex, BMI, disease duration, intensity of pain (VAS 0–10), painful and swollen joints, and inflammatory indices, as well as C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR). Results: Of the 34 patients studied, 24 (70.6%) presented NP to the ID-Pain questionnaire. According to DN4, 14 (41.2%) patients had NP, while using the PainDETECT questionnaire, 67.6% had NP. Patients with NP were statistically younger and had a higher VAS pain score compared to subjects without NP. The ENoG and median nerve ultrasound were normal in 81% of patients, while four patients had carpal tunnel syndrome. The ID-Pain questionnaire correlated with the number of painful joints (r = 0.48, p = 0.03) and with the AUSCAN questionnaire (r = 0.37, p = 0.05). The DN4 questionnaire correlated with PainDETECT (r = 0.58, p < 0.01). The PainDETECT questionnaire correlated with VAS pain (r = 0.49, p = 0.02), the DN4 questionnaire (r = 0.58, p < 0.01), and AUSCAN (r = 0.51, p = 0.02). The NPSI questionnaire correlated negatively with BMI (r = −0.53, p = 0.01) and positively with the PainDETECT questionnaire (r = 0.49, p = 0.02). Conclusions: Our study revealed that 32% to 70% of EHOA patients exhibited symptoms consistent with NP, with observed variability depending on the questionnaire utilized. Despite patients frequently exhibiting symptoms compatible with NP, only 19% of patients presented alterations on ENoG and ultrasound examinations confirming CTS. This suggests a probable nociplastic component for pain in patients with EHOA, which warrants tailored treatment. In the present study, NP correlated with clinical and functional indices of EHOA. [ABSTRACT FROM AUTHOR]

The role of calcium pyrophosphate (CPP) crystals in osteoarthritis (OA) is still a matter of debate. With this study we aimed to investigate the inflammatory features of synovial fluid (SF) collected from patients with OA with CPP crystals compared with those without crystals. We also explored the effect of OA SF on monocytes response. SFs were collected from adult patients with OA and subdivided according to the presence of crystals. Local cellular and humoral inflammatory mediators were analysed in the SF samples. The expression levels of IL-1β, IL-18, CASP-1, NLRP3, and GAPDH were measured by RT-PCR in the cells obtained by pelleting the SF samples. For the in vitro study, a monocytic cell line was treated with selected SF samples. SF with CPP crystals showed a significant increase in inflammatory cellular indices and higher levels of IL-1β, IL-8, and caspase-1 transcript with respect to SF without crystals. Higher concentrations of VEGF were also observed in the early stages of the whole OA patients. THP-1 cells stimulated with OA SF released a significant amount of IL-1 β in culture supernatants. This study demonstrated that SF collected from patients with OA shows different inflammatory features depending on the presence of CPP crystals. [ABSTRACT FROM AUTHOR]

Our study aimed to evaluate the association between fetuin-A levels and the presence of radiographic sacroiliitis and syndesmophytes in patients with early axial spondyloarthritis (axSpA) and to identify potential predictors of radiographic damage in the sacroiliac joints (SIJs) after 24 months. Patients diagnosed with axSpA in the Italian cohort of the SpondyloArthritis-Caught-Early (SPACE) study were included. Physical examinations, laboratory tests (including fetuin-A), SIJ,+ and spinal X-rays and MRIs at T0 (diagnosis) and at T24 were considered. Radiographic damage in the SIJs was defined according to the modified New York criteria (mNY). Fifty-seven patients were included in this analysis (41.2% male, median (interquartile range), chronic back pain [CBP] duration of 12 (8–18) months). Fetuin-A levels were significantly lower in patients with radiographic sacroiliitis compared to those without at T0 (207.9 (181.7–215.9) vs. 239.9 (217.9–286.9), respectively, p < 0.001) and at T24 (207.6 (182.5–246.5) vs. 261.1 (210.2–286.6) µg/mL, p = 0.03). At T0, fetuin-A levels were significantly higher in non-smokers, in patients with heel enthesitis and in those with a family history of axSpA; fetuin-A levels at T24 were higher in females, in patients with higher ESR or CRP at T0 and in those with radiographic sacroiliitis at T0. Fetuin-A levels at T0 were independently negatively associated with the likelihood of radiographic sacroiliitis (OR = 0.9 per 10-unit increase (95% CI 0.8, 0.999), p = 0.048); but not with the presence of syndesmophytes. After adjustment for confounders, fetuin-A levels at T0 and T24 were also negatively associated with mNY at T0 (β −0.5, p < 0.001) and at T24 (β −0.3, p < 0.001), respectively. Among other variables at T0, fetuin-A levels did not achieve statistical significance in predicting mNY at T24. Fetuin-A levels were negatively associated with radiographic damage of the SIJs, but not of the spine, in early axSpA and after 2 years of follow-up. Our findings suggest that fetuin-A levels may serve as a biomarker to identify patients with a higher risk of developing severe disease and early structural damage. [ABSTRACT FROM AUTHOR]

(1) Background: Synovial tissue plays a fundamental role in inflammatory processes. Therefore, understanding the mechanisms regulating healthy and diseased synovium functions, as in rheumatic diseases, is crucial to discovering more effective therapies to minimize or prevent pathological progress. The present study aimed at developing a bioartificial synovial tissue as an in vitro model for drug screening or personalized medicine applications using 3D bioprinting technology. (2) Methods: The volumetric extrusion technique has been used to fabricate cell-laden scaffolds. Gelatin Methacryloyl (GelMA), widely applied in regenerative medicine and tissue engineering, was selected as a bioink and combined with an immortalized cell line of fibroblast-like synoviocytes (K4IM). (3) Results: Three different GelMA formulations, 7.5–10–12.5% w/v, were tested for the fabrication of the scaffold with the desired morphology and internal architecture. GelMA 10% w/v was chosen and combined with K4IM cells to fabricate scaffolds that showed high cell viability and negligible cytotoxicity for up to 14 days tested by Live & Dead and lactate dehydrogenase assays. (4) Conclusions: We successfully 3D bioprinted synoviocytes-laden scaffolds as a proof-of-concept (PoC) towards the fabrication of a 3D synovial membrane model suitable for in vitro studies. However, further research is needed to reproduce the complexity of the synovial microenvironment to better mimic the physiological condition. [ABSTRACT FROM AUTHOR]

Background: The aim of the study was to examine the relationship among patients' characteristics, intraoperative pathology and pre/post-operative symptoms in a cohort of patients undergoing arthroscopic partial meniscectomy for symptomatic meniscal tears. Methods: Clinical data were collected (age, sex, body mass index, time to surgery, trauma). Intraoperative cartilage pathology was assessed with Outerbridge score. Meniscal tears were graded with the ISAKOS classification. Synovial inflammation was scored using the Macro-score. Patient symptoms were assessed pre/post-operatively using the KOOS instrument. Results: In the series of 109 patients (median age 47 years), 50% of the meniscal tears were traumatic; 85% of patients showed mild to moderate synovitis; 52 (47.7%) patients had multiple cartilage defects and 31 (28.4%) exhibited a single focal chondral lesion. Outerbridge scores significantly correlated with patient age, BMI and synovial inflammation. There was a correlation between severity of chondral pathology and high-grade synovial hyperplasia. Pre-operative KOOS correlated with BMI, meniscal degenerative changes and symptom duration. Obesity, time to surgery, presence of high-grade synovial hyperplasia and high-grade cartilage lesions were independent predictors of worse post-operative pain and function. Conclusion: We demonstrated that pre-operative symptoms and post-operative outcomes correlate with synovitis severity and cartilage pathology, particularly in old and obese patients that underwent arthroscopic partial meniscectomy. Importantly, patients with a degenerative meniscal pattern and with longer time to surgery experienced more severe cartilage damage and, consequentially, pain and dysfunction. These findings are fundamental to identify patients suitable for earlier interventions. [ABSTRACT FROM AUTHOR]

Several studies have investigated cartilage degeneration and inflammatory subchondral bone and synovial membrane changes using magnetic resonance (MR) in osteoarthritis (OA) patients. Conversely, there is a paucity of data exploring the role of knee ligaments, infrapatellar fat pad (IFP), and suprapatellar fat pad (SFP) in knee OA compared to post-traumatic cohorts of patients. Therefore, the aim of this study was to analyze the volumetric and morphometric characteristics of the following joint tissues: IFP (volume, surface, depth, femoral and tibial arch lengths), SFP (volume, surface, oblique, antero–posterior, and cranio–caudal lengths), anterior (ACL) and posterior cruciate ligament (PCL) (volume, surface, and length), and patellar ligament (PL) (volume, surface, arc, depth, and length). Eighty-nine MR images were collected in the following three groups: (a) 32 patients with meniscal tears, (b) 29 patients with ACL rupture (ACLR), and (c) 28 patients affected by end-stage OA. Volume, surface, and length of both ACL and PCL were determined in groups a and c. A statistical decrease of IFP volume, surface, depth, femoral and tibial arch lengths was found in end-stage OA compared to patients with meniscal tear (p = 0.002, p = 0.008, p < 0.0001, p = 0.028 and p < 0.001, respectively) and patients with ACLR (p < 0.0001, p < 0.0001, p = 0.008 and p = 0.011, respectively). An increment of volume and surface SFP was observed in group b compared to both groups a and c, while no differences were found in oblique, antero–posterior, and cranio–caudal lengths of SFP among the groups. No statistical differences were highlighted comparing volume, surface, arc, and length of PL between the groups, while PL depth was observed to be decreased in end-OA patients compared with meniscal tear patients (p = 0.023). No statistical differences were observed comparing ACL and PCL lengths between patients undergoing meniscectomy and TKR. Our study confirms that IFP MR morphometric characteristics are different between controls and OA, supporting an important role of IFP in OA pathology and progression in accordance with previously published studies. In addition, PL depth changes seem to be associated with OA pathology. Multivariate analysis confirmed that OA patients had a smaller IFP compared to patients with meniscal tears, confirming its involvement in OA. [ABSTRACT FROM AUTHOR]

The menisci exert a prominent role in joint stabilization and in the distribution of mechanical loading. Meniscal damage is associated with increased risk of knee OA. The aim of this study was to characterize the synovial membrane and meniscal tissues in patients undergoing arthroscopic partial meniscectomy for meniscal tear and to evaluate association with clinical outcomes. A total of 109 patients were recruited. Demographic and clinical data were collected. Visual Analogic Scale (VAS) measuring pain and Knee injury and Osteoarthritis Outcome Score (KOOS) were recorded at baseline and at 2-years follow-up. Histological and immunohistochemical characterizations were performed on synovial membranes and meniscal tissues. More than half of the patients demonstrated synovial mononuclear cell infiltration and hyperplasia. Synovial fibrosis was present in most of the patients; marked vascularity and CD68 positivity were observed. Inflammation had an impact on both pain and knee symptoms. Patients with synovial inflammation had higher values of pre-operative VAS and inflammation. Higher pre-operative pain was observed in patients with meniscal MMP-13 production. In conclusion, multivariate analysis showed that synovial inflammation was associated with pre-operative total KOOS scores, knee symptoms, and pain. Moreover, meniscal MMP-13 expression was found to be associated with pre-operative pain in multivariate analysis. Thus, targeting inflammation of the synovial membrane and meniscus might reduce clinical symptoms and dysfunction at the time of surgery. [ABSTRACT FROM AUTHOR]

The article discusses research which investigated the efficacy of ultrasound-guided glucocorticoid (GC) intra-articular injections in addressing pain and swelling associated with erosive hand osteoarthritis (EHOA). Topics explored include the physical examination of patients that participated in the study, the GC dosage administered, and the outcomes recorded particularly the safety demonstrated by the treatment.

Axial spondyloarthritis (axSpA) is a group of debilitating, chronic, rheumatic conditions characterized by inflammation and new bone formation, mainly involving the spine and the sacroiliac joints. The lack of biomarkers in axSpA is well known. Despite significant treatment advances in recent years thanks to the introduction of drugs with a new mode of action, such as new biologic and targeted synthetic disease-modifying antirheumatic drugs, no relevant improvement in the identification of disease biomarkers has been achieved. Common parameters, such as erythrocyte sedimentation rate and C-reactive protein, which are routinely used to measure systemic inflammation, are the sole markers available to date and are not adequate to assess disease activity in all patients. The aim of this study is to review the most promising serum biomarkers that may help treatment decision in axSpA via a proper assessment of disease activity and identification of negative prognostic factors. [ABSTRACT FROM AUTHOR]

Objectives: Our study aimed to identify: (1) the prevalence of spine and pelvis magnetic resonance imaging (MRI-spine and MRI-SIJ) inflammatory and structural lesions in patients (pts) with a diagnosis of axial spondyloarthritis (axSpA); (2) the predictive factors for a severe disease pattern with a higher probability of radiographic progression. Materials and Methods: Seventy-five pts with low back pain (LBP) (≥3 months, ≤2 years, onset ≤45 years) underwent physical examination, questionnaires, laboratory tests, X-rays, MRI-spine, and MRI-SIJ at baseline (T0) and during a 24-months follow-up. Two expert rheumatologists made axSpA diagnosis and classification (according ASAS criteria). MRI-spine, MRI-SIJ and X-rays were scored independently by 2 readers following the SPARCC, mSASSS, and mNY-criteria. According to ASAS criteria, 21 pts fulfilled imaging arm only and 29 clinical arm with/without imaging arm; 25 pts did not fulfill ASAS criteria. Results: At T0 the mean ± SD LBP onset was 28.51 ± 8.05 years, 45.3% pts were male, 38.7% were HLA-B27+; 56% showed bone marrow oedema (BMO) at MRI-spine and 64% at MRI-SIJ. Signs of enthesitis were found in 58% pts in the thoracic spine. Eighteen (24%) pts presented BMO at MRI-spine with a negative MRI-SIJ. The prevalence of BMO lesions and the SPARCC SIJ and spine score decreased during the follow-up in the 2 cohorts meeting ASAS criteria. An early onset of LBP, a lower use of NSAIDs, a BASDAI>4 were identified as predictors of spine structural damage; the high SPARCC SIJ score appeared to be a predictor of SIJ structural damage. A higher mSASSS was predicted by a lower age of onset of LBP. Predictor of higher SPARCC spine was a higher NSAIDs and of higher SPARCC SIJ score the HLA-B27 positivity with increased inflammatory biomarkers. Conclusions: At T0 a significant prevalence of BMO lesions was observed both in SIJ and spine, with predominant involvement of thoracic district. Since positive MRI-spine images were observed in the absence of sacroiliitis, these findings seem to be relevant in the axSpA diagnosis. Early age of disease onset, long duration of LBP, increased inflammatory biomarkers, higher use of NSAIDs, male gender, HLA-B27 positivity, SPARCC SIJ score>2 appeared predictors of radiological damage and activity. [ABSTRACT FROM AUTHOR]

Objective: To evaluate mid‐term radiographic and functional outcomes of tibial plateau fracture (TPF) patients treated with the open reduction internal fixation (ORIF) technique and to find predictive factors of clinical outcomes. Methods: A retrospective, single‐center study was performed enrolling a consecutive series of patients with diagnosis of TPF. All subjects were treated by ORIF between January 2010 and December 2015 at our level‐1 healthcare trauma center. The inclusion criteria were: age between 18 and 75 years; ORIF technique used for articular TPF, type 41‐B and 41‐C, isolated or with associated injuries. The patients were divided in two groups, according to fracture patterns and compared. Their characteristics, radiographic and clinical outcomes were recorded. Radiographs 12 months after surgery were evaluated for reduction and alignment, and radiographs at 24 months to describe post‐traumatic osteoarthritis (PTOA). Functional outcomes were assessed using the visual analog scale (VAS), the Short Form 36 (SF‐36), the knee injury and osteoarthritis outcome score (KOOS), and the American Knee Society score (AKSS) questionnaires. Return to work and sport activities were also investigated. Univariate and multivariate analysis were performed, and the statistical significance was defined as two‐tailed P < 0.05. Results: Forty‐five patients were included, 29 males and 16 females; the mean age was 54.5 years. The mean follow‐up was 57.18 months (range, 26–94). There were AO 41‐B fractures (partial articular fractures) in more than half of the patients (66.67%), while the remaining 15 had AO 41‐C fractures (complete articular fractures). The sub‐type AO 41‐B3 was the most common, reported in 62.22% of patients. The mean KOOS score was 69.0. Mean AKSS and SF‐36 PCS scores were 79.0 and 41.4, respectively. There were significant relationships between age and functional results (KOOS ADL, Sport, QoL, and SF‐36 PCS) and between BMI and KOOS Pain, ADL, Sport, and QoL. No differences were found between the two types of fractures regarding quality of reduction and alignment. AO 41‐C TPF tend to develop PTOA more frequently with respect to 41‐B fractures, while type AO 41‐C TPF had the worst clinical outcomes. We found that the presence of an articular step‐off and the malalignment of the tibial axis after surgery were predictive of daily pain felt by patients. PTOA was predictive of a worse AKSS. The overall complication rate was 13.33%: 1 superficial wound infection, 1 deep vein thrombosis, and 4 cases of transitory deficit of the common peroneal nerve. Conclusion: The present study demonstrates that early radiographic features may be predictive for pain perceived by patients at mid‐term follow‐up. [ABSTRACT FROM AUTHOR]

Patients with psoriatic arthritis (PsA) have an increased prevalence of obesity, but mechanisms underlying this association remain unknown and it is unclear if obesity is the cause or effect of PsA. For PsA patients, comorbid obesity may influence their clinical response to systemic treatment, and especially targeted immunomodulators such as anti-tumor necrosis factor (TNF)α. Weight gain has also been associated with anti-TNFα treatment. Consequently, modification of the therapeutic approach may be needed for patients with an inadequate response to TNFα inhibitors. In recent years, interleukin (IL)-12/IL-23 inhibitors have entered clinical practice as a new class of drug for the treatment of PsA, with some data suggesting a lower effect of body weight on their effectiveness. Recent findings demonstrate effective and sustained responses in patients with PsA to ustekinumab, an IL-12/IL-23 inhibitor. This narrative review critically discusses the link between PsA, obesity, and response to therapy. The current role of ustekinumab in this setting is also discussed. [ABSTRACT FROM AUTHOR]

The aim of this study was to identify the molecules and pathways involved in the cross‐talk between meniscus and synovium that may play a critical role in osteoarthritis (OA) pathophysiology. Samples of synovium and meniscus were collected from patients with early and end‐stage OA and cultured alone or cocultured. Cytokines, chemokines, metalloproteases, and their inhibitors were evaluated at the gene and protein levels. The extracellular matrix (ECM) changes were also investigated. In early OA cultures, higher levels of interleukin‐6 (IL‐6) and IL‐8 messenger RNA were expressed by synovium and meniscus in coculture compared with meniscus cultured alone. RANTES release was significantly increased when the two tissues were cocultured compared with meniscus cultured alone. Increased levels of matrix metalloproteinase‐3 (MMP‐3) and MMP‐10 proteins, as well as increased release of glycosaminoglycans and aggrecan CS846 epitope, were observed when synovium was cocultured with meniscus. In end‐stage OA cultures, increased levels of IL‐8 and monocyte chemoattractant protein‐1 (MCP‐1) proteins were released in cocultures compared with cultures of meniscus alone. Chemokine (C‐C motif) ligand 21 (CCL21) protein release was higher in meniscus cultured alone and in coculture compared with synovium cultured alone. Increased levels of MMP‐3 and 10 proteins were observed when tissues were cocultured compared with meniscus cultured alone. Aggrecan CS846 epitope release was increased in cocultures compared with cultures of either tissue cultured alone. Our study showed the production of inflammatory molecules by synovium and meniscus which could trigger inflammatory signals in early OA patients, and induce ECM loss in the progressive and final stages of OA pathology. Inflammatory mediators, metalloproteinases, and metalloproteinases inhibitors are produced by meniscus and synovium from early and end‐stage osteoarthritic patients. Production of inflammatory molecules by synovium and meniscus can trigger inflammatory signals in early osteoarthritis (OA) patients, and induce extracellular matrix loss in the progressive and final stages of OA pathology. The interaction between synovium and meniscus is suggested in early and late osteoarthritic patients and it may provide a basis for identifying the mechanisms contributing to the development of OA associated with meniscal tear. [ABSTRACT FROM AUTHOR]

The infrapatellar fat pad (IFP) is an intracapsular but extrasynovial structure, located between the patellar tendon, the femoral condyles and the tibial plateau. It consists of white adipose tissue, organised in lobules defined by thin connective septa. The aim of this study is the morphometric and ultrasonographic analysis of IFP in subjects without knee pathology during flexion‐extension movements. The morphometric study was conducted on 20 cadavers (15M, 5F, mean age 80.2 years). Ultrasound was performed on 24 volunteers with no history of knee diseases (5M, 19F, mean age: 45 years). The characteristics of the adipose lobules near the patellar tendon and in the deep portion of the IFP were evaluated. Numerical models were provided, according to the size of the lobules. At histological examination, the adipose lobules located near the patellar tendon were larger (mean area 12.2 mm2 ± 5.3) than those at a deeper level (mean area 1.34 mm2 ± 0.7, P < 0.001) and the thickness of the septa of the deepest adipose lobules (mean value 0.35 mm ± 0.32) was greater than that of the superficial one (mean value 0.29 mm ± 0.25, P < 0.001). At ultrasound, the IFP was seen to be composed of very large lobules in the superficial part (mean area 0.29 cm2 ± 0.17 in extension), with a significant reduction in flexion (mean area 0.12 cm2 ± 0.07, P < 0.01). The deep lobules were smaller (mean area 0.11 cm2 ± 0.08 in extension) and did not change their values (mean area 0.19 cm2 ± 0.52 in flexion, P > 0.05). In the sagittal plane, the reduction of thickness of the superficial layer (with large adipose lobules) during flexion was 20.6%, whereas that of the deep layer (with small adipose lobules) was 1.3%. Numerical simulation of vertical loads, corresponding to flexion of the knee, showed that stress mainly developed within the interlobular septa and opposed bulging of the lobules. The characteristics of the lobular arrangement of the IFP (large lobules with superficial septa in the superficial part and small lobules with thick septa in the deep one), significant changes in the areas and perimeters of the superficial lobules, and the reduced thickness of the superficial layer during flexion all indicate the dynamic role played by the IFP in knee kinematics. [ABSTRACT FROM AUTHOR]

Osteoarthritis (OA) is the most common form of joint disease and a major cause of pain and disability in the adult population. Interestingly, there are patients with symptomatic OA displaying pain, while patients with asymptomatic OA that do not experience pain but show radiographic signs of joint damage. Pain is a complex experience integrating sensory, affective, and cognitive processes related to several peripheral and central nociceptive factors besides inflammation. During the last years, the role of infrapatellar fat pad (IFP), other than the synovial membrane, has been investigated as a potential source of pain in OA. Interestingly, new findings suggest that IFP and synovial membrane might act as a functional unit in OA pathogenesis and pain. The present review discuss the role of IFP and synovial membrane in the development of OA, with a particular focus on pain onset and the possible involved mediators that may play a role in OA pathology and pain mechanisms. Inflammation of IFP and synovial membrane may drive peripheral and central sensitization in KOA. Since sensitization is associated with pain severity in knee OA and may potentially contribute to the transition from acute to chronic, persistent pain in knee OA, preventing sensitization would be a potentially effective and novel means of preventing worsening of pain in knee OA. [ABSTRACT FROM AUTHOR]

Aim: 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. Materials and methods: 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. Results: 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 IFP. MMP-10 was present only in CM of cartilage and synovial tissues. IL-1β, IL-15, TNF-α, CCL5, and CCL19 were undetectable. However, only K4IM cells stimulated by the CM from OA synovium showed an increase of IL-6, CXCL-8, CCL21, MMP10, and IL-1β expression. Conclusion: Our study showed that K4IM might be a suitable in vitro model for evaluating different cellular pathways in OA studies. Importantly, we demonstrated that in OA, all joint tissues might be involved in the progression of synovitis with a predominant role of synovial membrane itself compared to the other joint tissues. [ABSTRACT FROM AUTHOR]