Infrapatellar Fat Pad Research Articles

Role of joint adipose tissues in osteoarthritis

Osteoarthritis (OA) is the most common musculoskeletal disease, without any curative treatment. Obesity being the main modifiable risk factor for OA, much attention focused on the role of adipose tissues (AT). In addition to the involvement of visceral and subcutaneous AT via systemic ways, many arguments also highlight the involvement of local AT, present in joint tissues. Local AT include intra-articular AT (IAAT), which border the synovium, and bone marrow AT (BMAT) localized within marrow cavities in the bones. This review describes the known features and involvement of IAAT and BMAT in joint homeostasis and OA. Recent findings evidence that alteration in magnetic resonance imaging signal intensity of infrapatellar fat pad can be predictive of the development and progression of knee OA. IAAT and synovium are partners of the same functional unit; IAAT playing an early and pivotal role in synovial inflammation and fibrosis and OA pain. BMAT, whose functions have only recently begun to be studied, is in close functional interaction with its microenvironment. The volume and molecular profile of BMAT change according to the pathophysiological context, enabling fine regulation of haematopoiesis and bone metabolism. Although its role in OA has not yet been studied, the localization of BMAT, its functions and the importance of the bone remodelling processes that occur in OA argue in favour of a role for BMAT in OA.

Effect of isometric quadriceps exercise on local microcirculation of the infrapatellar fat pad in female patients with knee osteoarthritis

ObjectiveTo elucidate the local microcirculation of the infrapatellar fat pad (IFP) in patients with knee osteoarthritis (KOA) by determining the changes in IFP hardness and hemoglobin concentration during isometric quadriceps exercise (IQE). DesignIn this observational cross-sectional study, patients diagnosed with bilateral KOA were included in the KOA group (30 knees), healthy older adults in the control group (20 knees), and younger adults in the young group (20 knees). Ultrasonography was performed at rest and during IQE to measure IFP hardness based on shear wave velocity. Near-infrared spectroscopy was performed to measure oxygenated hemoglobin (O2Hb), deoxygenated hemoglobin (HHb), and total hemoglobin (cHb) in the IFP before (Baseline), during (IQE task), and after IQE (Post). IFP hardness and O2Hb, HHb, and cHb concentration were analyzed using a linear mixed model for the groups and measurement points. ResultsDuring IQE, IFP hardness changes were significantly less in the KOA group than in the other groups (KOA: 95% confidence intervals (CIs) [−0.854, 0.028]; control: 95% CI [−0.941, −0.341]; and young: 95% CI [−2.305, −1.706]). In the KOA group, O2Hb concentration exhibited no significant changes at Post compared with Baseline; however, significant changes were observed in the other groups (KOA: 95% CI [−1.176, 0.423]; control: 95% CI [−1.452, −0.276]; and young: 95% CI [−4.062, −2.102]). ConclusionsDuring IQE, changes in hardness and hemoglobin concentration in the IFP were not significant in the KOA group, suggesting impaired local microcirculation of the IFP.

Proteomic and lipidomic landscape of the infrapatellar fat pad and its clinical significance in knee osteoarthritis

Osteoarthritis (OA) is a prevalent joint disease that can be exacerbated by lipid metabolism disorders. The intra-articular fat pad (IFP) has emerged as an active participant in the pathological changes of knee OA (KOA). However, the proteomic and lipidomic differences between IFP tissues from KOA and control individuals remain unclear. Samples of IFP were collected from individuals with and without OA (n = 6, n = 6). Subsequently, these samples underwent liquid chromatography/mass spectrometry-based label-free quantitative proteomic and lipidomic analysis to identify differentially expressed proteins (DEPs) and lipid metabolites (DELMs). The DEPs were further subjected to enrichment analysis, and hub DEPs were identified using multiple algorithms. Additionally, an OA diagnostic model was constructed based on the identified hub DEPs or DELMs. Furthermore, CIBERSORT was utilized to investigate the correlation between hub protein expression and immune-related modules in IFP of OA. Our results revealed the presence of 315 DEPs and eight DELMs in IFP of OA patients compared to the control group. Enrichment analysis of DEPs highlighted potential alterations in pathways related to coagulation, complement, fatty acid metabolism, and adipogenesis. The diagnostic model incorporating four hub DEPs (AUC = 0.861) or eight DELMs (AUC = 0.917) exhibited excellent clinical validity for diagnosing OA. Furthermore, the hub DEPs were found to be associated with immune dysfunction in IFP of OA. This study presents a distinct proteomic and lipidomic landscape of IFP between individuals with OA and those without. These findings provide valuable insights into the molecular changes associated with potential mechanisms underlying OA.

Comparative characteristics of the stem cells’ number in the stromal vascular fraction of infrapatellar fat pad and subcutaneous fat tissue

ObjectivesThe use of infrapatellar fat pad adipose stem cells (IPFP-ASCs) shows an age-independent proliferation and differentiation potential. In addition, the pronounced chondrogenic potential of IPFP-ASCs makes them promising candidates for research for use in other methods of regenerative therapy. The purpose of this study was to ascertain the presence and compare the relative abundance of cells exhibiting an immunohistochemical profile characteristic of adipose-derived mesenchymal stem cells in selected samples of the stromal vascular fraction (SVF) obtained from the IPFP and subcutaneous fat tissue. MethodsA direct immunohistochemical study was carried out in serial paraffin sections of the SVF of the infrapatellar fat pad (IPFP) and subcutaneous tissue, using monoclonal antibodies. The minimum criteria were established by the International Society for Cell Therapy to ensure the identity of mesenchymal stem cells use CD73, CD90, and CD105 as positive markers and CD34, CD31, and CD45 as a negative. ResultsAccording to the results of histological, immunohistochemical, morphometric, and statistical studies, it was found that in the SVF of IPFP and subcutaneous adipose tissue, the relative number of cells with the profile CD105+, CD73+, CD34+, CD31−, CD45− in the standard field of view (×200), the SVF of IPFP was 1.58%, whereas the SVF of subcutaneous adipose tissue was 6.92 %, which was statistically significantly greater by 4.38 times (p ​< ​0.05). ConclusionThe presence of a sufficient number of mesenchymal stromal cells in IPFP in combination with their topographic relationship with the structures of the joint determines the use of the SVF of the IPFP for the treatment of diseases of the knee joint. Level of evidenceIII.

CORR Insights®: Human Infrapatellar Fat Pad Mesenchymal Stem Cell-derived Extracellular Vesicles Purified by Anion Exchange Chromatography Suppress Osteoarthritis Progression in a Mouse Model.

CORR Insights®: Human Infrapatellar Fat Pad Mesenchymal Stem Cell-derived Extracellular Vesicles Purified by Anion Exchange Chromatography Suppress Osteoarthritis Progression in a Mouse Model.

Associating Knee Osteoarthritis Progression with Temporal-Regional Graph Convolutional Network Analysis on MR Images.

Artificial intelligence shows promise in assessing knee osteoarthritis (OA) progression on MR images, but faces challenges in accuracy and interpretability. To introduce a temporal-regional graph convolutional network (TRGCN) on MR images to study the association between knee OA progression status and network outcome. Retrospective. 194 OA progressors (mean age, 62 ± 9 years) and 406 controls (mean age, 61 ± 9 years) from the OA Initiative were randomly divided into training (80%) and testing (20%) cohorts. Sagittal 2D IW-TSE-FS (IW) and 3D-DESS-WE (DESS) at 3T. Anatomical subregions of cartilage, subchondral bone, meniscus, and the infrapatellar fat pad at baseline, 12-month, and 24-month were automatically segmented and served as inputs to form compartment-based graphs for a TRGCN model, which containing both regional and temporal information. The performance of models based on (i) clinical variables alone, (ii) radiologist score alone, (iii) combined features (containing i and ii), (iv) composite TRGCN (combining TRGCN, i and ii), (v) radiomics features, (vi) convolutional neural network based on Densenet-169 were compared. DeLong test was performed to compare the areas under the ROC curve (AUC) of all models. Additionally, interpretability analysis was done to evaluate the contributions of individual regions. A P value <0.05 was considered significant. The composite TRGCN outperformed all other models with AUCs of 0.841 (DESS) and 0.856 (IW) in the testing cohort (all P < 0.05). Interpretability analysis highlighted cartilage's importance over other structures (42%-45%), tibiofemoral joint's (TFJ) dominance over patellofemoral joint (PFJ) (58%-67% vs. 12%-37%), and importance scores changes in compartments over time (TFJ vs. PFJ: baseline: 44% vs. 43%, 12-month: 52% vs. 39%, 24-month: 31% vs. 48%). The composite TRGCN, capturing temporal and regional information, demonstrated superior discriminative ability compared with other methods, providing interpretable insights for identifying knee OA progression. Stage 2.

Effect of Low-Intensity Pulsed Ultrasound on Macrophage Properties and Fibrosis in the Infrapatellar Fat Pad in a Carrageenan-Induced Knee Osteoarthritis Rat Model.

In the progression of knee osteoarthritis (KOA), fibrosis of the infrapatellar fat pad (IFP) is a key pathological change. Low-intensity pulsed ultrasound (LIPUS) inhibits IFP fibrosis by decreasing the gene expression and activity of hypoxia-inducible factor (HIF-1α), which is a protein involved in IFP fibrosis in KOA rat models. On the other hand, macrophages play an important role in the progression of fibrosis in various tissues, and LIPUS irradiation suppresses macrophage infiltration and inflammatory cytokine secretion. However, whether LIPUS suppresses macrophage polarity and IFP fibrosis in KOA remains unclear. Therefore, we investigated the effect of LIPUS on macrophage polarity and IFP fibrosis. A KOA model was created by injecting carrageenin into the bilateral knee joints of Wistar rats (eight weeks old). Tissues were harvested over time for histological and molecular biological analysis. The KOA model was also subjected to LIPUS irradiation for two weeks following the injection of carrageenin. RM-4-positive cells were widely distributed in IFP two weeks after carrageenin administration, but M2 macrophages were significantly increased, and the Sirius red area was decreased in the LIPUS-irradiated group compared with those in the non-irradiated group. The gene expression of M1 macrophage markers was significantly decreased and that of M2 macrophage markers was significantly increased in the LIPUS-irradiated group. The expression of transforming growth factor-β (TGF-β) and type 1 collagen was also significantly decreased. These results suggest that LIPUS may serve as a novel approach for the treatment of KOA through its effect on M1 macrophages and suppression of TGF-β expression.

Human Infrapatellar Fat Pad Mesenchymal Stem Cell-derived Extracellular Vesicles Purified by Anion Exchange Chromatography Suppress Osteoarthritis Progression in a Mouse Model.

Human Infrapatellar Fat Pad Mesenchymal Stem Cell-derived Extracellular Vesicles Purified by Anion Exchange Chromatography Suppress Osteoarthritis Progression in a Mouse Model.

Effect of weight loss on knee joint synovitis over 48 months and mediation by subcutaneous fat around the knee: data from the Osteoarthritis Initiative

BackgroundObesity influences the development of osteoarthritis via low-grade inflammation. Progression of local inflammation (= synovitis) increased with weight gain in overweight and obese women compared to stable weight. Synovitis could be associated with subcutaneous fat (SCF) around the knee. Purpose of the study was to investigate the effect of weight loss on synovitis progression and to assess whether SCF around the knee mediates the relationship between weight loss and synovitis progression.MethodsWe included 234 overweight and obese participants (body mass index [BMI] ≥ 25 kg/m2) from the Osteoarthritis Initiative (OAI) with > 10% weight loss (n = 117) or stable overweight (< ± 3% change, n = 117) over 48 months matched for age and sex. In magnetic resonance imaging (MRI) at baseline and 48 months, effusion-synovitis and Hoffa-synovitis using the MRI Osteoarthritis Knee Score (MOAKS) and average joint-adjacent SCF (ajSCF) were assessed. Odds-ratios (ORs) for synovitis progression over 48 months (≥ 1 score increase) were calculated in logistic regression models adjusting for age, sex, baseline BMI, Physical Activity Scale for the Elderly (PASE), and baseline SCF measurements. Mediation of the effect of weight loss on synovitis progression by local SCF change was assessed.ResultsOdds for effusion-synovitis progression decreased with weight loss and ajSCF decrease (odds ratio [OR] = 0.61 and 0.56 per standard deviation [SD] change, 95% confidence interval [CI] 0.44, 0.83 and 0.40, 0.79, p = 0.002 and 0.001, respectively), whereas odds for Hoffa-synovitis progression increased with weight loss and ajSCF decrease (OR = 1.47 and 1.48, CI 1.05, 2.04 and 1.02, 2.13, p = 0.024 and 0.038, respectively). AjSCF decrease mediated 39% of the effect of weight loss on effusion-synovitis progression.ConclusionsEffusion-synovitis progression was slowed by weight loss and decrease in local subcutaneous fat. Hoffa-synovitis characterized by fluid in the infrapatellar fat pad increased at the same time, suggesting a decreasing fat pad rather than active synovitis. Decrease in local subcutaneous fat partially mediated the systemic effect of weight loss on synovitis.

PLOD2 gene expression in infrapatellar fat pad is correlated with fat mass in obese patients with end-stage knee osteoarthritis

ObjectiveTo investigate associations between obesity-linked systemic factors and gene expression indicative for the inflammatory and fibrotic processes in the infrapatellar fat pad (IFP), in a population of obese patients with end-stage knee osteoarthritis (KOA). MethodsWe collected human IFPs from 48 patients with a mean body mass index (BMI) of 35.44 ​kg/m2 during total knee replacement procedures. These patients were part of a randomized controlled trial and met the criteria of having OA and a BMI of ≥30 ​kg/m2. Blood samples were collected to assess serum levels of glucose, total cholesterol, HDL cholesterol, LDL cholesterol, triglycerides, and leptin. Total body composition was measured using dual-energy X-ray absorptiometry. Gene expressions of IL6, TNFA, COL1A1, IL1B, ASMA, PLOD2 in the IFP were analyzed. ResultsUnivariate analysis resulted in a positive correlation between BMI and procollagen-lysine,2-oxoglutarate 5-dioxygenase 2 (PLOD2) expression (r2 ​= ​0.13). In univariate analyses of obesity-linked systemic factors and PLOD2, significant correlations were found for lean mass (r2 ​= ​0.20), fat mass (r2 ​= ​0.20), serum cholesterol (r2 ​= ​0.17), serum triglycerides (r2 ​= ​0.19) and serum leptin (r2 ​= ​0.10). A multiple linear regression model indicated fat mass to be a strong predictor of PLOD2 production in the IFP (r2 ​= ​0.22, P ​= ​0.003). ConclusionOur study demonstrates the positive association between fat mass and PLOD2 expression in the IFP of obese end-stage knee OA patients. This may indicate that within this patient population the fibrotic process in the IFP is influenced by systemic adipose tissue, next to local inflammatory processes.

Single cell transcriptome profiling of infrapatellar fat pad highlights the role of interstitial inflammatory fibroblasts in osteoarthritis

ObjectivesOsteoarthritis (OA) is a whole-joint disease in which the role of the infrapatellar fat pad (IFP) in its pathogenesis is unclear. Our study explored the cellular heterogeneity of IFP to understand OA and identify therapeutic targets. MethodsSingle-cell and single-nuclei RNA sequencing were used to analyze 10 IFP samples, comprising 5 from OA patients and 5 from healthy controls. Analyses included differential gene expression, enrichment, pseudotime trajectory, and cellular communication, along with comparative studies with visceral and subcutaneous fats. Key subcluster and pathways were validated using multiplex immunohistochemistry. ResultsThe scRNA-seq performed on the IFPs of the OA and control group profiled the gene expressions of over 49,674 cells belonging to 11 major cell types. We discovered that adipose stem and progenitor cells (ASPCs), contributing to the formation of both adipocytes and synovial-lining fibroblasts (SLF). Interstitial inflammatory fibroblasts (iiFBs) were a subcluster of ASPCs that exhibit notable pro-inflammatory and proliferative characteristics. We identified four adipocyte subtypes, with one subtype showing a reduced lipid synthesis ability. Furthermore, iiFBs modulated the activities of macrophages and T cells in the IFP. Compared to subcutaneous and visceral adipose tissues, iiFBs represented a distinctive subpopulation of ASPCs in IFP that regulated cartilage proliferation through the MK pathway. ConclusionThis study presents a comprehensive single-cell transcriptomic atlas of IFP, uncovering its complex cellular landscape and potential impact on OA progression. Our findings highlight the role of iiFBs in OA, especially through MK pathway, opening new avenues for understanding OA pathogenesis and developing novel targeted therapies.

High Rates of Abnormal Patellofemoral Morphology in Adolescents With Anterior Knee Pain: A Retrospective Review.

Background: Anterior knee pain is a common reason for referral to a pediatric orthopedic surgeon. Although previous studies have found that adults with anatomic risk factors for patellofemoral instability (patella dislocation) are predisposed to anterior knee pain, no studies have elucidated the relationship between anatomic risk factors for patellofemoral instability and anterior knee pain in children. Purpose: We sought to characterize common radiographic findings in adolescent patients with a chief complaint of anterior knee pain and to determine the prevalence of abnormal patellofemoral morphology. Methods: We conducted a retrospective review of patients 13 to 18 years old with anterior knee pain at a single tertiary care metropolitan institution from 2016 to 2021. X-rays and magnetic resonance imaging (MRI) were evaluated in those diagnosed with "chondromalacia patellae," "chondromalacia," "patellofemoral disorders," or "anterior knee pain." Patella alta, tibial tubercle-trochlear groove (TT-TG) distance, tubercle height, Wiberg patella type, patellar tilt, and trochlear dysplasia characterization were recorded. Results: Of the 293 adolescents with anterior knee pain included, 62 had bilateral anterior knee pain. Of the 172 MRIs, 72 (42%) met criteria for patella alta, Caton-Deschamps Index (CDI) >1.3, 35% had a TT-TG distance >15 mm, and 32% had lateral patellar tilt >15°. Magnetic resonance imaging findings included infrapatellar fat pad signal hyperintensity (41%) and patellofemoral dysplasia (23%). Of all 293 adolescents, 74% had images showing abnormal patellofemoral morphology, of which 30% had a history of 1 or more patellar dislocation. Overall, 40% of the adolescents had surgery, most commonly medial patellofemoral ligament (MPFL) reconstruction (18%). Conclusions: In this retrospective review, nearly 3/4 of adolescents with anterior knee pain had images showing abnormal patellofemoral morphology, including patella alta, increased TT-TG distance, trochlear dysplasia, or abnormal lateral patellar tilt; only 18% had MPFL surgery. These findings suggest that primary care providers might consider obtaining X-rays and/or MRIs to evaluate for pathology that warrants orthopedic evaluation.

Modification of Mesenchymal Stem/Stromal Cell-Derived Small Extracellular Vesicles by Calcitonin Gene Related Peptide (CGRP) Antagonist: Potential Implications for Inflammation and Pain Reversal.

During the progression of knee osteoarthritis (OA), the synovium and infrapatellar fat pad (IFP) can serve as source for Substance P (SP) and calcitonin gene-related peptide (CGRP), two important pain-transmitting, immune, and inflammation modulating neuropeptides. Our previous studies showed that infrapatellar fat pad-derived mesenchymal stem/stromal cells (MSC) acquire a potent immunomodulatory phenotype and actively degrade Substance P via CD10 both in vitro and in vivo. On this basis, our hypothesis is that CD10-bound IFP-MSC sEVs can be engineered to target CGRP while retaining their anti-inflammatory phenotype. Herein, human IFP-MSC cultures were transduced with an adeno-associated virus (AAV) vector carrying a GFP-labelled gene for a CGRP antagonist peptide (aCGRP). The GFP positive aCGRP IFP-MSC were isolated and their sEVs' miRNA and protein cargos were assessed using multiplex methods. Our results showed that purified aCGRP IFP-MSC cultures yielded sEVs with cargo of 147 distinct MSC-related miRNAs. Reactome analysis of miRNAs detected in these sEVs revealed strong involvement in the regulation of target genes involved in pathways that control pain, inflammation and cartilage homeostasis. Protein array of the sEVs cargo demonstrated high presence of key immunomodulatory and reparative proteins. Stimulated macrophages exposed to aCGRP IFP-MSC sEVs demonstrated a switch towards an alternate M2 status. Also, stimulated cortical neurons exposed to aCGRP IFP-MSC sEVs modulate their molecular pain signaling profile. Collectively, our data suggest that yielded sEVs can putatively target CGRP in vivo, while containing potent anti-inflammatory and analgesic cargo, suggesting the promise for novel sEVs-based therapeutic approaches to diseases such as OA.

The effect of plasma cytokines on the expression of adiponectin and its receptors in the synovial membrane of joints and the infrapatellar fat pad in patients with rheumatoid arthritis and osteoarthritis

BackgroundRheumatoid arthritis (RA) is an autoimmune inflammatory disease that leads to joint destruction. Numerous pro-inflammatory mediators, including adipokines, play an important role in the pathogenesis of RA. ObjectiveThe aim of the study was to investigate the relationships between selected plasma cytokines and expression of adiponectin and its receptors in the synovium and the infrapatellar fat pad in patients with RA and osteoarthritis (OA). MethodsBlood, synovium and fat pad samples from 18 patients with RA and 18 with OA were collected during joint replacement surgery. Spearman rank correlations between plasma concentrations of selected cytokines (IL-1β, IL-2, IL-4, IL-6, IL-7, IL-8, IL-10, IL-12 p40, IL-13, IL-17, G-CSF and GM-CSF) and the expression of adiponectin and its receptors were determined. Plasma levels of cytokines were determined using a magnetic bead-based multiplex assay, mRNA expression of adiponectin and its receptors were determined by real-time PCR. ResultsIn OA patients, there were significant positive correlations between adiponectin expression in the synovial membrane and plasma levels of IL-1β, IL-4, G-CSF and GM-CSF, as well as a significant positive correlation between adiponectin expression in the fat pad and plasma levels of GM-CSF. In addition, OA patients showed significant negative correlations between AdipoR1 and AdipoR2 expression in the synovial membrane and plasma IL-6 levels, as well as between AdipoR2 expression in the synovial membrane and plasma MCP-1 and TNF-α levels. In patients with RA, there were no significant correlations between adiponectin expression in the synovial membrane and infrapatellar fat pad and plasma levels of the cytokines studied. In addition, RA patients showed a statistically significant negative correlation between AdipoR1 expression in the synovial membrane and plasma levels of TNF-α, IL-7, IL-12 and IL-13, and a significant negative correlation between AdipoR1 expression in the infrapatellar fat pad and plasma levels of IL-1β. ConclusionsAdiponectin and its receptors showed the correlations with several plasma cytokines, however, a thorough understanding of the role of adiponectin in RA and OA requires further investigation.

Sex-specific effects of injury and beta-adrenergic activation on metabolic and inflammatory mediators in a murine model of post-traumatic osteoarthritis

ObjectiveMetabolic processes are intricately linked to the resolution of innate inflammation and tissue repair, two critical steps for treating post-traumatic osteoarthritis (PTOA). Based on lipolytic and immunoregulatory actions of norepinephrine, we hypothesized that intra-articular β-adrenergic receptor (βAR) stimulation would suppress PTOA-associated inflammation in the infrapatellar fat pad (IFP) and synovium. DesignWe used the βAR agonist isoproterenol to perturb intra-articular metabolism 3.5 weeks after applying a non-invasive single-load compression injury to knees of 12-week-old male and female mice. We examined the acute effects of intra-articular isoproterenol treatment relative to saline on IFP histology, multiplex gene expression of synovium-IFP tissue, synovial fluid metabolomics, and mechanical allodynia. ResultsInjured knees developed PTOA pathology characterized by heterotopic ossification, articular cartilage loss, and IFP atrophy and fibrosis. Isoproterenol suppressed the upregulation of pro-fibrotic genes and downregulated the expression of adipose genes and pro-inflammatory genes (Adam17, Cd14, Icam1, Csf1r, and Casp1) in injured joints of female (but not male) mice. Analysis of published single-cell RNA-seq data identified elevated catecholamine-associated gene expression in resident-like synovial-IFP macrophages after injury. Injury substantially altered synovial fluid metabolites by increasing amino acids, peptides, sphingolipids, phospholipids, bile acids, and dicarboxylic acids, but these changes were not appreciably altered by isoproterenol. Intra-articular injection of either isoproterenol or saline increased mechanical allodynia in female mice, whereas neither substance affected male mice. ConclusionsAcute βAR activation altered synovial-IFP transcription in a sex and injury-dependent manner, suggesting that women with PTOA may be more sensitive than men to treatments targeting sympathetic neural signaling pathways.

Lateral Parapatellar Approach with Preservation Infrapatellar Fat Pad in TKA for Severe Valgus Deformity with Flexion Contracture and Patella Subluxation: A Case Report

Lateral Parapatellar Approach with Preservation Infrapatellar Fat Pad in TKA for Severe Valgus Deformity with Flexion Contracture and Patella Subluxation: A Case Report

Qualitative and Quantitative Measures in the Infrapatellar Fat Pad in Older Adults: Associations with Knee Pain, Radiographic Osteoarthritis, Kinematics, and Kinetics of the Knee

ObjectiveThe purpose of this study is to delineate cross-sectional associations between qualitative and quantitative measures of the infrapatellar fat pad (IPFP) and knee symptoms, structure, kinematics, and kinetics in older adults. MethodsNinety eligible subjects (90 knees, mean age 54.0 years, 68.9% female) were examined at our centre. We used T2-weighted fat-suppressed magnetic resonance imaging (MRI) to evaluate signal intensity alteration, maximum sagittal area, and depth of the IPFP. Symptomatic osteoarthritis (SOA) was a pain subscale score greater than 0 on the Western Ontario McMaster Osteoarthritis Index. A Kellgren-Lawrence grade ≥ 2 identified incident radiographic osteoarthritis (iROA). Three-dimensional gait data were employed to analyze knee joint kinematics and kinetics. Correlation and regression analyses assessed associations between IPFP measurements and SOA, iROA, kinematics, and kinetics. ResultsThere were strong and positive associations between IPFP signal intensity alteration and both SOA and iROA in multivariable regression analyses [OR (95% CI): 2.849 (1.440 to 5.636), 2.356 (1.236 to 4.492), respectively]. Conversely, a significant negative correlation was observed between IPFP maximum area and flexion angle [B (95%CI): -1.557 (-2.549 to -0.564)]. Moreover, adjusting for covariates did not reveal any significant correlation between IPFP parameters and other indicators (P > 0.05, respectively). ConclusionIPFP signal intensity alteration and area were associated with knee clinical symptoms, structural abnormalities, and flexion angle in adults over 40, respectively. These findings suggest that IPFP may be a crucial imaging biomarker in early and middle knee osteoarthritis.

Broken-fat pad sign: a characteristic radiographic finding to distinguish between knee rheumatoid arthritis and osteoarthritis.

Diagnostic imaging plays an important role in the pre-treatment workup of knee osteoarthritis (OA) and rheumatoid arthritis (RA). Herein, we identified a useful MRI sign of infrapatellar fat pad (IPFP) to improve diagnosis. Eighty-one age- and sex-matched RA and OA patients each, with pathological diagnosis and pre-treatment MRI were retrospectively evaluated. All randomized MR images were blinded and independently reviewed by two radiologists. The assessment process included initial diagnosis, sign evaluation, and final diagnosis, with a 3-week interval between each assessment. Broken-fat pad (BFP) sign was assessed on sagittal T2-weighted-imaging in routine MRI. The area under the curve and Cohen's kappa (κ) were used to assess the classification performance. Two shape features were extracted from IPFP for quantitative interpretation. The median age of the study population was 57.6 years (range: 31.0-78.0 years). The BFP sign was detected more frequently in patients with RA (72.8%) than those with OA (21.0%). Both radiologists achieved better performance by referring to the BFP sign, with accuracies increasing from 58.0 to 75.9% and 72.8 to 79.6%, respectively. The inter-reader correlation coefficient showed an increase from fair (κ = 0.30) to substantial (κ = 0.75) upon the consideration of the BFP sign. For quantitative analysis, the IPFP of RA had significantly lower sphericity (0.54 ± 0.04 vs. 0.59 ± 0.03, p < 0.01). Despite larger surface-volume-ratio of RA (0.38 ± 0.05 vs. 0.37 ± 0.04, p = 0.25) than that of OA, there was no statistical difference. The BFP sign is a potentially important diagnostic clue for differentiating RA from OA with routine MRI and reducing misdiagnosis. With the simple and feasible broken-fat pad sign, clinicians can help more patients with early accurate diagnosis and proper treatment, which may be a valuable addition to the diagnostic workup of knee MRI assessment. • Detailed identification of infrapatellar fat pad alterations of patients may be currently ignored in routine evaluation. • Broken-fat pad sign is helpful for differentiating rheumatoid arthritis and osteoarthritis. • The quantitative shape features of the infrapatellar fat pad may provide a possible explanation of the signs. • This sign has good inter-reader agreements and is feasible for clinical application.

Ultrasound assessment of the infrapatellar fat pad can detect Hoffa-synovitis in patients following anterior cruciate ligament reconstruction: A pilot study

IntroductionOsteoarthritis (OA) commonly occurs following anterior cruciate ligament reconstruction (ACLR), affecting over 50 % of patients within 10–15 years post-ACLR. The Hoffa-synovitis of the infrapatellar fat pad (IPFP) has been implicated as a major contributor to OA pathogenesis. While MRI is typically used to evaluate the IPFP, it is cost-prohibitive for routine screening. This study aimed to validate ultrasound as an alternative for detecting IPFP Hoffa-synovitis in participants post-ACLR. MethodsIn this cross-sectional study, 15 participants (18–35 years, 1–5 years post-ACLR) underwent two imaging sessions separated by one week. First, a standardized bilateral anterior knee ultrasound assessment was used to examine IPFP echo-intensity. Second, MRI scans of both knees were graded by a board-certified musculoskeletal radiologist for Hoffa-synovitis according to the Anterior Cruciate Ligament Osteoarthritis Score grading system. IPFP echo-intensity were quantified on each ultrasound image, and a limb symmetry index (LSI) was calculated to assess between-limb differences. We used an independent t-test and Cohen's d effect sizes to compare IPFP echo-intensity LSI between people with and without MRI-confirmed Hoffa-synovitis. ResultsFour of the 15 participants (27 %) exhibited MRI-confirmed Hoffa-synovitis. Significantly higher IPFP echo-intensity LSI values were found in participants with Hoffa-synovitis (32.1 ± 12.1 %) compared to those without (10.5 ± 10.4 %), confirming the ultrasound's ability to distinguish between the two groups (t = -3.44; p = 0.004; d = 2.01). DiscussionUltrasound detects bilateral IPFP signal intensity alterations in participants post-ACLR with MRI-confirmed Hoffa-synovitis. This work should be seen as a proof-of-concept, and further validation in a larger, more diverse sample is essential for verifying these results.

Infrapatellar fat pad adipose tissue-derived macrophages display a predominant CD11c+CD206+ phenotype and express genotypes attributable to key features of OA pathogenesis.

In knee osteoarthritis (OA), macrophages are the most predominant immune cells that infiltrate synovial tissues and infrapatellar fat pads (IPFPs). Both M1 and M2 macrophages have been described, but their role in OA has not been fully investigated. Therefore, we investigated macrophage subpopulations in IPFPs and synovial tissues of knee OA patients and their correlation with disease severity, examined their transcriptomics, and tested for factors that influenced their polarization. Synovial tissues and IPFPs were obtained from knee OA patients undergoing total knee arthroplasty. Macrophages isolated from these joint tissues were characterized via flow cytometry. Transcriptomic profiling of each macrophage subpopulations was performed using NanoString technology. Peripheral blood monocyte-derived macrophages (MDMs) were treated with synovial fluid and synovial tissue- and IPFP-conditioned media. Synovial fluid-treated MDMs were treated with platelet-rich plasma (PRP) and its effects on macrophage polarization were observed. Our findings show that CD11c+CD206+ macrophages were predominant in IPFPs and synovial tissues compared to other macrophage subpopulations (CD11c+CD206-, CD11c-CD206+, and CD11c-CD206- macrophages) of knee OA patients. The abundance of macrophages in IPFPs reflected those in synovial tissues but did not correlate with disease severity as determined from Mankin scoring of cartilage destruction. Our transcriptomics data demonstrated highly expressed genes that were related to OA pathogenesis in CD11c+CD206+ macrophages than CD11c+CD206-, CD11c-CD206+, and CD11c-CD206- macrophages. In addition, MDMs treated with synovial fluid, synovial tissue-conditioned media, or IPFP-conditioned media resulted in different polarization profiles of MDMs. IPFP-conditioned media induced increases in CD86+CD206+ MDMs, whereas synovial tissue-conditioned media induced increases in CD86+CD206- MDMs. Synovial fluid treatment (at 1:8 dilution) induced a very subtle polarization in each macrophage subpopulation. PRP was able to shift macrophage subpopulations and partially reverse the profiles of synovial fluid-treated MDMs. Our study provides an insight on the phenotypes and genotypes of macrophages found in IPFPs and synovial tissues of knee OA patients. We also show that the microenvironment plays a role in driving macrophages to polarize differently and shifting macrophage profiles can be reversed by PRP.