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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]

Abstract: The infrapatellar pad, a fibro‐adipose tissue with peculiar microscopic and mechanical features, is gaining wide attention in the field of rheumatological research. The purpose of this descriptive review is to summarize the most recent published evidence on the anatomic, physiologic and biomechanical inter‐relationship between the infrapatellar fat pad and the knee synovial membrane. As an extrasynovial tissue, the infrapatellar fat pad does not directly interact with the articular cartilage; based on its location in close contact with the synovial membrane, and due to the metabolic properties of adipose tissue, it may influence the behavior of the synovial membrane. In fact, considering evidence of macroscopic and microscopic anatomy, the infrapatellar fat pad is the site of insertion of the infrapatellar and medial synovial plicae. Also biochemically, there is much evidence highlighting the interaction among these two structures; in the case of inflammation, the mutual interplay is ascribable to the release of pro‐inflammatory mediators stimulating the proliferation of inflammatory cells and promoting tissue modifications in both. All these assumptions could support the emerging idea that the infrapatellar fat pad and the synovial membrane may be considered a morpho‐functional unit. [ABSTRACT FROM AUTHOR]

Objective. The infrapatellar fat pad (IFP) is considered a local producer of adipocytokines, suggesting a potential role in OA. The objective of this study was to evaluate the histopathological and molecular characteristics of OA IFPs compared with controls. Methods. The histopathological characteristics of IFPs were evaluated in patients undergoing total knee replacements and in control patients (without OA), considering the following parameters: presence of inflammatory cells, vascularization, adipose lobules dimension and thickness of the interlobular septa. Immunohistochemistry was performed to evaluate VEGF, monocyte chemotactic protein 1 (MCP-1) and IL-6 proteins. Quantitative real time PCR was performed to evaluate the expression levels of adipocytokines in the OA IFPs. Results. OA IFPs showed an increase in inflammatory infiltration, vascularization and thickness of the interlobular septa compared with controls. VEGF, MCP-1 and IL-6 proteins were higher in OA IFPs compared with in controls. Inflammatory infiltration, hyperplasia, vascularization and fibrosis were increased in OA IFP synovial membranes compared with in those of controls. VEGF protein levels were associated with an increased number of vessels in the OA IFPs, while MCP-1 and IL-6 protein levels were associated with higher grades of inflammatory infiltration. Leptin levels were positively correlated with adiponectin and MCP-1expression, while adiponectin positively correlated with peroxisome proliferative activated receptor gamma, MCP-1 and IFP vascularity. MCP-1 showed a positive correlation with peroxisome proliferative activated receptor gamma. IFP lobules dimensions were positively correlated with IL-6 expression and negatively with thickness of interlobular septa. VEGF mRNA levels were positively correlated with increased synovial vascularity. Conclusions: OA IFPs and synovial membranes are more inflamed, vascularized and fibrous compared with those of control patients (without OA). [ABSTRACT FROM AUTHOR]

Osteoarthritis is a common chronic joint disorder affecting older people. The knee is the major joint affected. The symptoms of osteoarthritis include limited range of motion, joint swelling, and pain causing disability. There are no disease modifying drugs available, and treatments are mainly focused on pain management. Total knee replacement performed at the end stage of the disease is considered the only cure available. It has been found that obese people have an increased risk to develop not only knee but also hand osteoarthritis. This supports the concept that adipose tissue might be related to osteoarthritis not only through overloading. As matter of fact, obesity induces a low grade systemic inflammatory state characterized by the production and secretion of several adipocytokines that may have a role in osteoarthritis development. Furthermore, hypertension, impaired glucose, and lipid metabolism, which are comorbidities associated with obesity, have been shown to alter the joint tissue homeostasis. Moreover, infrapatellar fat pad in the knee has been demonstrated to be a local source of adipocytokines and potentially contribute to osteoarthritis pathogenesis. Here, we discuss the role of systemic and local adipose tissue in knee osteoarthritis. J. Cell. Physiol. 232: 1971-1978, 2017. © 2016 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

The extrasynovial adipose tissue Infrapatellar Fat Pad (IFP) is an emerging player in knee osteoarthritis (OA) [1,2]. While the role of constitutive adipocytes in secreting cytokines is known, little awareness on origin/function of the stem cells component exists. This study aims to isolate/characterize IFP-derived stem cells (IFP-dSCs) from OA patients investigating their role in disease development. IFP samples were processed to discard matrix and the adipocyte fraction. The resulting pellet was resuspended in proliferative medium and cultured routinely. IFP-dSCs morphology and ultrastructure were observed by optical microscope and Transmission Electron Microscope (TEM); expansion potential of cells was assessed by a population doubling level assay. IFP-dSCs vitality was assessed using a Apoptotic/Necrotic/Healthy Cells Detection Kit, while the metabolic activity of cell cultures was analysed by MTT assay. Flow cytometry analysis was performed to identify the presence of specific markers; in particular, IFP-dSCs were stained with antibodies against CD73/105/90/44/34/106, IL-6R/1R, VEGFR2. At last, IFP-dSCs plasticity was also assessed, evaluating their commitment towards the adipogenic, chondrogenic and endothelial lineages. IFP-dSCs isolation required 14 h; cells were fibroblast-like and typically spindle shaped at low density, showing a greater polygonal nucleus at high density. Semithin-sections stained with toluidine blue revealed vesicles in the cytoplasm, as confirmed by TEM analysis. These rounded formations of electrondense material were in proximity of empty round vesicles and in some contact areas a partial fusion between the external membranes was appreciable. An exponential growth during the entire long-term expansion period was observed, with a replication time of 42.7 ± 3.8 h. From passage (P)8 to P20, cells performed 11.9 ± 0.9 population doublings. IFP-dSCs immunophenotype was positive for the investigated markers, suggesting a role in modulation of inflammation; interestingly, cells were 100% CD73+bright both at low and high P in colture. Preliminary data about plasticity revealed the ability in differentiating towards adipogenic and endothelial lineages. Further analysis will be required to assess chondrogenic commitment. Experimental evidence on IFP-dSCs seem to correlate histopathological features of IFP in OA (i.e. thickening of interlobular septa, increase in vascularization and innervation) with the stem cell component. [ABSTRACT FROM AUTHOR]

The suprapatellar fat pad (SFP) is located above the patella and behind the suprapatellar joint recess with the function of increasing the congruency of the extensor mechanism. Osteoarthritis SFP has been demonstrated to produce high amount of inflammatory molecules and to be more fibrous than subcutaneous adipose tissue in osteoarthritis (OA) patients. The aim of this study was to analyze 1. the morphological characteristics of the SFP compared to that of the infrapatellar fat pad (IFP) in normal subjects; 2. the magnetic resonance (MR) volumetric characteristics of the IFP and the SFP in non-OA controls compared to moderate and endstage OA patients. Five specimens of SFP were sampled from bodies of the donation program of the University of Padova without history of OA. The SFP consisted of white adipose tissue, of lobular type, with lobules delimited by thin connective septa. Forty-four MR images were collected: a) 17 control; b) 15 patients with moderate OA ; and c) 12 patients with end-stage OA. Volume, depth, femoral and tibial arch lengths of IFP were quantified. The SFP volume, oblique, antero-posterior and, cranio-caudal lengths were determined. A decrease of IFP volume, depth, femoral, and tibial arch lengths in moderate and end-stage OA compared to controls were observed. A difference in IFP hypointense signal was found between groups. No differences were found in SFP characteristics between the groups. In controls and moderate OA patients, correlations were found among the different MRI characteristics of both IFP and SFP, while in the end-stage OA group correlations were found only in SFP. Differences of the IFP MRI morphometric characteristics between the groups analyzed supports an important role of IFP in OA pathology and progression. On the contrary, no differences were highlighted in SFP analysis suggesting that this fat pad is not clearly involved in OA, probably due to its peculiar localization and different function. [ABSTRACT FROM AUTHOR]

The infrapatellar fat pad (IFP) is an adipose tissue present in the knee that lies between the patella, femur, meniscus and tibia, filling the space between these structures. IFP facilitates the distribution of the synovial fluid and may act to absorb impulsive actions generated through the joint. IFP in osteoarthritis (OA) pathology undergoes structural changes characterized by inflammation, hypertrophy and fibrosis. The aim of the present study is to analyze the mechanical behavior of the IFP in patients affected by end-stage OA. A specific test fixture was designed and indentation tests were performed on IFP specimens harvested from OA patients who underwent total knee arthroplasty. Experiments allowed to assess the typical features of mechanical response, such as non-linear stress–strain behavior and time-dependent effects. Results from mechanical experimentations were implemented within the framework of a visco-hyperelastic constitutive theory, with the aim to provide data for computational modelling of OA IFP role in knee mechanics. Initial and final indentation stiffness were calculated for all subjects and statistical results reveled that OA IFP mechanics was not significantly influenced by gender, BMI and sample preparation. OA IFP mechanical behavior was also compared to that of other adipose tissues. OA IFP appeared to be a stiffer adipose tissue compared to subcutaneous, visceral adipose tissues and heel fat pads. It is reasonable that fibrosis induces a modification of the tissue destabilizing the normal distribution of forces in the joint during movement, causing a worsening of the disease. [ABSTRACT FROM AUTHOR]