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This study aimed to investigate the biochemical effects of osteoarthritic infrapatellar fat pad (IPFP) on cartilage and the underlying mechanisms. Human IPFP and articular cartilage were collected from end-stage osteoarthritis (OA) patients during total knee arthroplasty. IPFP-derived fat-conditioned medium (FCM) was used to stimulate human primary chondrocytes and cartilage explants. Functional effect of osteoarthritic IPFP was explored in human primary chondrocytes and articular cartilage in vitro and ex vivo. Activation of relative pathways and its effects on chondrocytes were assessed through immunoblotting and inhibition experiments, respectively. Neutralization test was performed to identify the main factors and their associated pathways responsible for the effects of IPFP. Osteoarthritic IPFP-derived FCM significantly induced extracellular matrix (ECM) degradation in both human primary chondrocytes and cartilage explants. Several pathways, such as NF-κB, mTORC1, p38MAPK, JNK, and ERK1/2 signaling, were significantly activated in human chondrocytes with osteoarthritic IPFP-derived FCM stimulation. Interestingly, inhibition of p38MAPK and ERK1/2 signaling pathway could alleviate the detrimental effects of FCM on chondrocytes, while inhibition of other signaling pathways had no similar results. In addition, IL-1β and TNF-α instead of IL-6 in osteoarthritic IPFP-derived FCM played key roles in cartilage degradation via activating p38MAPK rather than ERK1/2 signaling pathway. Osteoarthritic IPFP induces the degradation and inflammation of cartilage via activation of p38MAPK and ERK1/2 pathways, in which IL-1β and TNF-α act as the key factors. Our study suggests that modulating the effects of IPFP on cartilage may be a promising strategy for knee OA intervention.

To determine whether pericruciate fat pad (PCFP) signal intensity alteration and maximal area are associated with incident radiographic osteoarthritis (ROA) over 4 years in the Osteoarthritis Initiative (OAI) study. Participants were from the Osteoarthritis Initiative (OAI) study. Case knees (n = 355) were defined by incident ROA between 12 and 48 months visits and were matched by sex, age, and radiographic status with control knees (n = 355). Magnetic resonance images (MRIs) were used to assess PCFP signal intensity alteration and PCFP maximal area at P0 (time of onset of ROA), P-1 (1 year prior to P0), and baseline. Conditional logistic regression analyses were applied to assess associations between PCFP measures and the risk of incident ROA. The mean age of participants was 60.1 years and 66.9% were women. In multivariable analyses, PCFP signal intensity alteration measured at three time points (OR [95%CI]: 1.28 [1.10–1.50], 1.52 [1.30–1.78], 1.50 [1.27–1.76], respectively) and PCFP maximal area (OR [95%CI]: 1.21 [1.03–1.42], 1.27 [1.07–1.52], 1.37 [1.15–1.62], respectively) were significantly associated with incident ROA. PCFP signal intensity alteration and maximal area were associated with incident ROA over 4 years, implying that they may have roles to play in ROA. • Pericruciate fat pad signal intensity alteration and maximal area were associated with incident ROA, implying that they may have roles to play in ROA.

The aim of this study was to investigate cross-sectional associations between serum levels of IL-8 and the above outcomes in patients with knee osteoarthritis (OA).A total of 160 subjects with clinical knee OA were included. Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score and Lequesne index were used to assess the joint symptom. Magnetic resonance imaging was used to measure knee structural abnormalities including infrapatellar fat pad (IPFP) signal intensity alternation. Knee radiographic OA was assessed by radiography using the Kellgren-Lawrence (K-L) grading system. Enzyme-linked immunosorbent assay was used to measure the serum levels of IL-8 and cartilage or bone biomarkers.In multivariable analyses, serum IL-8 was positively associated with WOMAC weight-bearing pain (β 2.85, P = 0.028), WOMAC physical dysfunction (β 12.71, P = 0.048), and Lequesne index (β 1.65, P = 0.015), and had positive associations with IPFP signal intensity alteration (OR 3.18, P = 0.011) and serum levels of N-telopeptide of type I collagen (NTXI), N-terminal procollagen III propeptide (PIIINP), matrix metalloproteinase (MMP)3, and MMP13 (β 0.24-1.44, all P 0.05) in patients with clinical knee OA. Furthermore, there were positive associations between IL-8 and WOMAC score (β 22.49, P = 0.037), K-L grades (OR 3.88, P = 0.013), and IPFP signal intensity alteration (OR 3.20, P = 0.033) in patients with radiographic OA.Serum levels of IL-8 were positively associated with increased knee symptoms, IPFP signal intensity alteration, and serum levels of bone and/or cartilage biomarkers, suggesting that IL-8 may have a role to play in knee OA.Key Point• This study systemically investigates the associations between serum IL 8 and knee symptoms, joint structures, and cartilage or bone biomarkers in patients with knee osteoarthritis, and some significant associations have been found, suggesting that IL 8 may have a role to play in knee OA.

Background Osteoarthritis (OA) is a common chronic disease in older adults. Currently, there are no effective therapies to reduce disease severity and progression of knee OA (KOA), particularly in mid- to late-stages. This study aims to examine the effect of methotrexate (MTX) on knee effusion-synovitis and pain in symptomatic patients with mid- to late-stage KOA. Methods/design This protocol describes a multicentre randomised placebo-controlled clinical trial aiming to recruit 200 participants with mid- to late-stage symptomatic KOA and with effusion-synovitis grade of ≥ 2. Participants will be randomly allocated to the MTX group (start from 5 mg per week for the first 2 weeks and increase to 10 mg per week for the second 2 weeks and 15 mg per week for the remaining period if tolerated) or the placebo group. Primary outcomes are effusion-synovitis size measured by magnetic resonance imaging (MRI) and knee pain assessed by visual analogue scale (VAS). Secondary outcomes are signal intensity alteration within infrapatellar fat pad (IPFP) and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) total score and subscores, and the Outcome Measures in Rheumatology Arthritis Clinical Trials-Osteoarthritis Research Society International (OMERACT-OARSI) responders. Both intention-to-treat and per-protocol analyses will be performed. Discussion If MTX intervention can relieve symptoms and reduce inflammation in patients with mid- to late-stage KOA, it has the potential for significant clinical and public health impact as this low-cost and commonly used intervention would delay the time to knee replacement, leading to substantial cost savings and improve quality of life. Trial registration ClinicalTrials.gov NCT03815448. Registered on 21 January 2019.

Background There are few clinical and epidemiological studies reporting the association between abnormal changes within the IPFP and knee osteoarthritic changes. This study aims to describe the associations between hypointense signals in the infrapatellar fat pad (IPFP) and knee structural change and symptoms in older adults. Methods Participants (n = 874) were selected randomly from local community and followed up 2.7 years later (range 2.6–3.3 years). T1- or T2-weighted fat-suppressed magnetic resonance imaging (MRI) was assessed for IPFP hypointense signal, cartilage volume, cartilage defects, and bone marrow lesions (BMLs). Knee pain was assessed by self-administered Western Ontario and McMaster Osteoarthritis Index (WOMAC) questionnaire. Radiographic osteoarthritis was assessed using the OARSI atlas. Results Cross-sectionally, hypointense signals in the IPFP were significantly associated with a higher risk of knee cartilage defects at all sites, tibiofemoral BMLs and knee pain in multivariable analyses. Longitudinally, baseline signal abnormalities were significantly and positively associated with increases in knee cartilage defects (OR: 2.27, 95 % CI: 1.61–3.21), BMLs (OR: 1.91, 95 % CI: 1.39–2.62), and knee pain (OR: 1.36, 95 % CI: 1.05–1.76) in multivariable analyses. The associations with cartilage defects remained significant after adjustment for BMLs, but the associations with BMLs and knee pain decreased in magnitude or became non-significant after further adjustment for cartilage defects. Conclusions Hypointense signals in the IPFP were associated primarily with increased knee cartilage defects and also with BMLs and knee symptoms in cross-sectional and longitudinal analyses, suggesting the abnormality represented by this signal has a potentially important role in osteoarthritis progression. Electronic supplementary material The online version of this article (doi:10.1186/s13075-016-1130-y) contains supplementary material, which is available to authorized users.

Introduction Recent studies regarding the infrapatellar fat pad (IPFP) mainly focus on the roles of the cells derived from the IPFP. There have been few clinical or epidemiological studies reporting on the association between the IPFP and knee osteoarthritis (OA). Our objective is to generate hypotheses regarding the associations between IPFP maximum area and knee OA measures in older adults. Methods A total of 977 subjects between 50 and 80 years of age (mean, 62.4 years) participated in the study. Radiographic knee osteophyte and joint space narrowing (JSN) were assessed using the Osteoarthritis Research Society International atlas. T1- or T2-weighted fat suppressed magnetic resonance imaging (MRI) was utilized to assess IPFP maximum area, cartilage volume, cartilage defects, and bone marrow lesions (BMLs). Knee pain was assessed by self-administered Western Ontario McMaster Osteoarthritis Index (WOMAC) questionnaire. Results After adjustment for potential confounders, IPFP maximum area was significantly associated with joint space narrowing (odds ratio (OR): 0.75, 95% confidence interval (CI): 0.62 to 0.91 (medial), 0.77, 95% CI: 0.62 to 0.96 (lateral)) and medial osteophytes (OR: 0.52, 95% CI: 0.35 to 0.76), knee tibial and patellar cartilage volume (β: 56.9 to 164.9 mm3/cm2, all P

Introduction The role of popliteal cysts and subgastrocnemius bursitis in knee joint homeostasis is uncertain. The aim of this study is to describe cross-sectional associations between popliteal cysts, subgastrocnemius bursitis, knee symptoms and structural abnormalities in older adults. Methods A cross-sectional sample of 900 randomly-selected subjects (mean age 63 years, 48% female) were studied. Knee pain, stiffness and dysfunction were assessed by self-administered Western Ontario McMaster Osteoarthritis Index (WOMAC) questionnaire. Radiographic knee osteophyte and joint space narrowing (JSN) were recorded. Magnetic resonance imaging (MRI) was utilized to assess popliteal cysts, subgastrocnemius bursitis, cartilage defects and bone marrow lesions (BMLs). Results Popliteal cysts were present in 11.7% and subgastrocnemius bursitis in 12.7% of subjects. Subgastrocnemius bursitis was more common in those with popliteal cyst (36.2% versus 9.7%, P