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BACKGROUND: Overweight or obesity is the most significant risk factors for knee osteoarthritis. Time-restricted diet shows an effective effect in preventing overweight or obesity. Whether infrapatellar fat pad, an important component of the knee joint, is affected by time-restricted diet and thus influences knee osteoarthritis remains unclear. OBJECTIVE: To employ a high-fat diet-induced rat model to investigate the effect of weight loss by time-restricted diet on infrapatellar fat pad, thereby providing evidence for early prevention and treatment of obesity-related knee osteoarthritis. METHODS: Fifteen male Sprague-Dawley rats were randomly divided into three groups (n=5 per group). Rats in the control group were allowed to eat at will for 24 hours and were fed the defined control diet (12% fat); rats in the high-fat diet group were allowed to eat at will for 24 hours and were fed the high-fat diet (45% fat); and rats in the high-fat diet with time-restricted diet group were fed the high-fat diet only from 9:00 (2 hours after the light) to 17:00 (2 hours before the dark). After 8 weeks of feeding, mDixon-Quant sequence was used to assess proton density fat fraction in the infrapatellar fat pad and subcutaneous adipose tissue in the right inguinal region. ELISA was used to quantify differences adipokine. Sirius red staining was used to evaluate changes in fibrosis of the infrapatellar fat pad. The expressions of uncoupling protein-1 in the infrapatellar fat pad and subcutaneous adipose tissue in the right inguinal region as well as leptin, adiponectin and tumor necrosis factor-α in the infrapatellar fat pad were detected by immunohistochemistry staining. RESULTS AND CONCLUSION: After 8 weeks of feeding, compared with the high-fat diet group, the body mass of rats in the control group (P=0.036) and the high-fat diet with time-restricted diet group (P=0.003) was significantly reduced. The proton density fat fraction in the infrapatellar fat pad in the high-fat diet group was significantly higher than that in the control group (P < 0.001) and the high-fat diet with time-restricted diet group (P=0.004), while there was no significant difference in the proton density fat fraction of the subcutaneous adipose tissue among the three groups. The serum leptin levels of rats in the highfat diet group were significantly higher than those in the control group (P=0.030) and the high-fat diet with time-restricted diet group (P=0.018). Compared with the high-fat diet group, the infrapatellar fat pad fibrosis characterized by Sirius red staining in the control group (P < 0.001) and the time-restricted diet group (P=0.003) was significantly decreased. The expression of leptin in IFP of the high-fat diet group was significantly higher than that of the control group (P < 0.001) and the high-fat diet with time-restricted diet group (P < 0.001). The expression of adiponectin in the infrapatellar fat pad of the high-fat diet group was significantly lower than that of the control group (P=0.004) and the high-fat diet with time-restricted feeding group (P=0.048). However, there was no positive expression of uncoupling protein-1 in the infrapatellar fat pad and subcutaneous adipose tissue of all the three groups, and no positive expression of tumor necrosis factor-α in the infrapatellar fat pad. To conclude, time-restricted diet could retard the fibrosis of the infrapatellar fat pad, reduce the proton density fat fraction of the infrapatellar fat pad, and affect the level of adipokine in serum and infrapatellar fat pad. Time-restricted diet may become a simple and effective option for the treatment and prevention of obesity-related knee osteoarthritis. [ABSTRACT FROM AUTHOR]

Osteoarthritis (OA) is a major disease whose prevalence increases with aging, sedentary lifestyles, and obesity. The association between obesity and OA has been well documented, but the precise mechanisms underlying this heightened risk remain unclear. While obesity imposes greater forces on joints, systemic fat-derived factors such as lipids or adipokine may potentially act on the pathophysiology of OA, but the exact role of these factors in weight-bearing and non-weight-bearing joints remains elusive. Intra-articular adipose tissues (IAAT) have gained significant attention for actively participating in OA pathogenesis by interacting with various joint tissues. Lipid content has been proposed as a diagnostic target for early OA detection and a potential source of biomarkers. Moreover, targeting a specific IAAT called infrapatellar fat pad (IFP) and its lipids hold promise for attenuating OA-associated inflammation. Conversely, bone marrow adipose tissue (BMAT), which was long thought to be an inert filling tissue, is now increasingly considered a dynamic tissue whose volume and lipid content regulate bone remodeling in pathological conditions. Given OA's ability to alter adipose tissues, particularly those within the joint (IFP and BMAT), and the influence of adipose tissues on OA pathogenesis, this review examines the lipids produced by OA-associated adipose tissues, shedding light on their potential role in OA pathophysiology and highlighting them as potential therapeutic targets. • Dual relationship between lipids-adipose tissue and osteoarthritis drives disease progression. • Intra-articular fat pad aids Osteoarthritis; targeting its lipids reduces the inflammatory phenotype. • Bone marrow adipocytes might be new players in osteoarthritis pathophysiology. • Lipids from systemic and joint adipose tissues are potential biomarkers or therapeutic targets in osteoarthritis. [ABSTRACT FROM AUTHOR]

Obesity increases osteoarthritis (OA) risk due to adipose tissue dysfunction with associated metabolic syndrome and excess weight. Lipodystrophy syndromes exhibit systemic metabolic and inflammatory abnormalities similar to obesity without biomechanical overloading. Here, we used lipodystrophy mouse models to investigate the effects of systemic versus intra-articular adipose tissue dysfunction on the knee. Intra-articular adipose tissue development was studied using reporter mice. Mice with selective lipodystrophy of intra-articular adipose tissue were generated by conditional knockout (cKO) of Bscl2 in Gdf5 -lineage cells, and compared with whole-body Bscl2 knockout (KO) mice with generalised lipodystrophy and associated systemic metabolic dysfunction. OA was induced by surgically destabilising the medial meniscus (DMM) and obesity by high-fat diet (HFD). Gene expression was analysed by quantitative RT-PCR and tissues were analysed histologically. The infrapatellar fat pad (IFP), in contrast to overlying subcutaneous adipose tissue, developed from a template established from the Gdf5 -expressing joint interzone during late embryogenesis, and was populated shortly after birth by adipocytes stochastically arising from Pdgfrα -expressing Gdf5 -lineage progenitors. While female Bscl2 KO mice with generalised lipodystrophy developed spontaneous knee cartilage damage, Bscl2 cKO mice with intra-articular lipodystrophy did not, despite the presence of synovial hyperplasia and inflammation of the residual IFP. Furthermore, male Bscl2 cKO mice showed no worse cartilage damage after DMM. However, female Bscl2 cKO mice showed increased susceptibility to the cartilage-damaging effects of HFD-induced obesity. Our findings emphasise the prevalent role of systemic metabolic and inflammatory effects in impairing cartilage homeostasis, with a modulatory role for intra-articular adipose tissue. [ABSTRACT FROM AUTHOR]

Knee osteoarthritis (KOA) is a degenerative joint disease characterized by inflammation and cartilage degradation. The infrapatellar fat pad (IFP), located beneath the patella within the knee joint, serves as a key anatomical structure involved in cushioning and supporting the knee. It is also an active endocrine organ that secretes various bioactive substances, potentially influencing the local inflammatory environment and contributing to KOA pathogenesis. Netrin-4 (NTN4), a protein primarily known for its role in neuronal guidance, has been implicated in various non-neuronal functions, including inflammatory processes and tissue remodeling. This study aims to explore the involvement of NTN4 in KOA, focusing on its expression in the IFP and its potential impact on disease progression. This study involved 82 patients with radiographically confirmed KOA undergoing total knee arthroplasty (TKA). The correlation between NTN4 expression and OA pathology, including Kellgren–Lawrence (K/L) grades, was investigated. NTN4-expressing cells were identified in the stromal vascular fraction, including fibroblastic, hematopoietic, and endothelial cells of the IFP. To elucidate the molecular effects of NTN4, RNA sequencing (RNA-seq) was performed on fibroblastic cells treated with recombinant NTN4. Subsequent quantitative PCR (qPCR) was used to validate the RNA-seq findings. NTN4 expression was significantly elevated in the IFP of patients with advanced KOA (K/L grades 3 and 4) compared to those with early-stage disease (K/L grade 2). Higher NTN4 expression was found in fibroblastic cells, and RNA-seq analysis revealed upregulation of genes associated with pro-inflammatory pathways, including IL-17 and TNF-α signaling, and matrix degradation. Notably, genes including IL6, MMP1, CXCL1, and CXCL8 were significantly elevated, as confirmed by qPCR, indicating NTN4's role in promoting an inflammatory and catabolic environment. Our findings suggest that NTN4 plays a significant role in the pathogenesis of KOA by promoting inflammation and matrix degradation within the IFP. Although NTN4 expression was not directly correlated with clinical symptoms, its elevated expression in fibroblastic cells and influence on inflammatory and degradative pathways suggest a potential mechanism for exacerbating joint damage. Targeting NTN4 could offer a novel therapeutic approach to mitigating inflammation and slowing disease progression in KOA, ultimately improving patient outcomes. Further research is needed to clarify NTN4's specific roles and therapeutic potential in OA management. [ABSTRACT FROM AUTHOR]

Aims: Knee osteoarthritis (KOA) is a common degenerative joint disease characterized by pain and functional limitations. Current treatments offer symptomatic relief but do not address the underlying pathology. This study explores the role of the infrapatellar fat pad (IFP) in KOA and evaluates the efficacy of its partial arthroscopic excision. Methods: A retrospective review was conducted on 37 KOA patients who underwent partial IFP excision. Pain and function were assessed using the WOMAC and VAS scores, while MRI evaluations focused on cartilage health. Results: Significant postoperative improvements were observed in both pain and functional outcomes, with substantial reductions in WOMAC and VAS scores (P < 0.001). MRI findings demonstrated notable enhancements in cartilage integrity, reflected in significantly improved WORMS scores (P < 0.001). Conclusions: Partial excision of the IFP significantly reduces pain and improves function in KOA patients, while also promoting cartilage health. These findings support the IFP's role in KOA pathology and highlight the potential benefits of targeted surgical intervention. [ABSTRACT FROM AUTHOR]

To 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). In 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. During 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]). During IQE, changes in hardness and hemoglobin concentration in the IFP were not significant in the KOA group, suggesting impaired local microcirculation of the IFP. [ABSTRACT FROM AUTHOR]

Abstract Aims Knee osteoarthritis (KOA) is a common degenerative joint disease characterized by pain and functional limitations. Current treatments offer symptomatic relief but do not address the underlying pathology. This study explores the role of the infrapatellar fat pad (IFP) in KOA and evaluates the efficacy of its partial arthroscopic excision. Methods A retrospective review was conducted on 37 KOA patients who underwent partial IFP excision. Pain and function were assessed using the WOMAC and VAS scores, while MRI evaluations focused on cartilage health. Results Significant postoperative improvements were observed in both pain and functional outcomes, with substantial reductions in WOMAC and VAS scores (P

Ultrasound therapy effectively treats a joint range of motion limitation and pain originating from soft tissue in knee osteoarthritis (OA). Few interventional studies have focused on the infrapatellar fat pad (IFP), and the effects of high-intensity continuous ultrasound (HICUS) on IFP stiffness and gliding have not been investigated. Therefore, we aimed to determine the effects of HICUS on IFP stiffness and gliding. This single-blind, randomized, controlled crossover study involved 24 healthy participants. The HICUS and placebo conditions were applied to the knee joint on 2 different days. HICUS was performed (1 MHz, 2.5 W/cm², duty cycle 100%, 5 min) using an ultrasound machine equipped with an applicator and adsorption-type fixed automatic rotation irradiation function. The main outcomes were IFP stiffness and gliding measured at 10 degrees and 120 degrees knee flexion. Gliding was measured as the difference between the patellar-tendon tibial angles at 10 degrees and 120 degrees knee flexion. Measurements were performed before (T1), immediately after (T2), and 15 min after (T3) treatment. Two-way repeated measures analysis of variance showed a significant interaction of IFP stiffness at 10 degrees knee flexion; post-test results showed that HICUS decreased stiffness at T2 and T3. There was no significant difference at 120 degrees. A significant interaction of gliding was observed under the HICUS condition. Post-tests showed that HICUS significantly improved gliding at T2 and T3. HICUS is a simple, safe intervention for improving IFP stiffness and gliding in healthy participants, with sustained effects. Further studies are needed to evaluate its efficacy in patients. [ABSTRACT FROM AUTHOR]

Abstract Background Fibrosis of the infrapatellar fat pad (IFP) is a feature of osteoarthritis and contributes substantially to the pain and dysfunction in patients’ joints. However, the underlying mechanisms remain unclear. C-C motif chemokine ligand-2 (CCL2) plays a central role in tissue fibrosis. Thus, we aimed to investigate the role of CCL2 in the development of IFP fibrosis in a rat model of arthritis, hypothesizing that a CCL2 antagonist could mitigate fibrotic progression. Methods We induced arthritis in male Wistar rats using intra-articular injections of carrageenan. Furthermore, to evaluate the effects of a CCL2 antagonist on protein expression and collagen deposition in the IFP of the rats, we transferred an N-terminal-truncated CCL2 gene into a rat model via electroporation-mediated intramuscular injection. Macrophage infiltration and collagen deposition in the IFP were analyzed in vivo. Groups were compared using the Mann–Whitney U test and Student’s t-test. Results We identified infiltrating macrophages as well as increases in CCL2 and TGF-β levels as collagen deposition progressed. Gene transfer of the CCL2-antagonist before arthritis induction attenuated collagen deposition remarkably. Conclusions We provide initial evidence that anti-CCL2 gene therapy can effectively suppress the development of IFP fibrosis in a rat model. Thus, targeting CCL2 holds promise as a therapeutic strategy for managing tissue fibrosis in osteoarthritis patients.

Metabolic 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. We 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. Injured 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. Acute 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. [ABSTRACT FROM AUTHOR]

Background: Fibrosis of the infrapatellar fat pad (IFP) is a feature of osteoarthritis and contributes substantially to the pain and dysfunction in patients' joints. However, the underlying mechanisms remain unclear. C-C motif chemokine ligand-2 (CCL2) plays a central role in tissue fibrosis. Thus, we aimed to investigate the role of CCL2 in the development of IFP fibrosis in a rat model of arthritis, hypothesizing that a CCL2 antagonist could mitigate fibrotic progression. Methods: We induced arthritis in male Wistar rats using intra-articular injections of carrageenan. Furthermore, to evaluate the effects of a CCL2 antagonist on protein expression and collagen deposition in the IFP of the rats, we transferred an N-terminal-truncated CCL2 gene into a rat model via electroporation-mediated intramuscular injection. Macrophage infiltration and collagen deposition in the IFP were analyzed in vivo. Groups were compared using the Mann–Whitney U test and Student's t-test. Results: We identified infiltrating macrophages as well as increases in CCL2 and TGF-β levels as collagen deposition progressed. Gene transfer of the CCL2-antagonist before arthritis induction attenuated collagen deposition remarkably. Conclusions: We provide initial evidence that anti-CCL2 gene therapy can effectively suppress the development of IFP fibrosis in a rat model. Thus, targeting CCL2 holds promise as a therapeutic strategy for managing tissue fibrosis in osteoarthritis patients. [ABSTRACT FROM AUTHOR]

The 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. Ninety eligible subjects (90 knees, mean age 54.0 years, 68.9% female) were examined at our center. 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 analyzes assessed associations between IPFP measurements and SOA, iROA, kinematics, and kinetics. There were strong and positive associations between IPFP signal intensity alteration and both SOA and iROA in multivariable regression analyzes [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). IPFP 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. [ABSTRACT FROM AUTHOR]

Abstract Background The infrapatellar fat pad (IPFP) lies extrasynovial and intracapsular, preserving the joint cavity and serving as a biochemical regulator of inflammatory reactions. However, there is a lack of research on the relationship between anterior knee pain (AKP) and the IPFP after medial patellofemoral ligament reconstruction (MPFLR). Pinpointing the source of pain enables clinicians to promptly manage and intervene, facilitating personalized rehabilitation and improving patient prognosis. Methods A total of 181 patients were included in the study. These patients were divided into the AKP group (n = 37) and the control group (n = 144). Clinical outcomes included three pain-related scores, Tegner activity score, patient satisfaction, etc. Imaging outcomes included the IPFP thickness, IPFP fibrosis, and the IPFP thickness change and preservation ratio. Multivariate analysis was used to determine the independent factors associated with AKP. Finally, the correlation between independent factors and three pain-related scores was analyzed to verify the results. Results The control group had better postoperative pain-related scores and Tegner activity score than the AKP group (P 0.50, P

Introduction: Mature adipocyte-derived dedifferentiated fat cells (DFATs) represent a subtype of multipotent cells that exhibit comparable phenotypic and functional characteristics to adipose-derived stem cells (ASCs). In this study, we assessed the chondroprotective properties of intra-articularly administrated DFATs in a rat model of osteoarthritis (OA). We also investigated in vitro the expression of anti-inflammatory and chondroprotective genes in DFATs prepared from the infrapatellar fat pad (IFP) and subcutaneous adipose-tissue (SC) of human origin. Methods: In the cell transplantation experiment, rats were assigned to the DFAT and Control group (n = 10 in each group) and underwent anterior cruciate ligament transection (ACLT) accompanied by medial meniscus resection (MMx) to induce OA. One week later, they received intra-articular injections of 1 × 106 DFATs (DFAT group) or PBS (control group) four times, with a weekly administration frequency. Macroscopic and microscopic evaluations were conducted five weeks post-surgery. In the in vitro experiments. DFATs derived from the IFP (IFP-DFATs) and SC (SC-DFATs) were prepared from donor-matched tissue samples (n = 3). The gene expression of PTGS2, TNFAIP6, PRG4, BMP2, and BMP6 under TNF-α or IFN-γ stimulation in these cells was evaluated using RT-PCR. Furthermore, the effect of co-culturing synovial fibroblasts with DFATs on the gene expression of ADAMTS4 and IL-6 were evaluated. Results: Intra-articular injections of DFATs significantly inhibited cartilage degeneration in the rat OA model induced by ACLT and MMx. RT-PCR analysis revealed that both IFP-DFATs and SC-DFATs upregulated the expression of genes involved in immune regulation, anti-inflammation, and cartilage protection such as PTGS2, TNFAIP6, and BMP2, under stimulation by inflammatory cytokines. Co-culture with DFATs suppressed the expression of ADAMTS4 and IL6 in synovial fibroblasts. Conclusions: The intra-articular injection of DFATs resulted in chondroprotective effects in the rat OA model. Both SC-DFATs and IFP-DFATs induced the expression of anti-inflammatory and chondroprotective genes in vitro. These results indicate that DFATs appear to possess therapeutic potential in inhibiting cartilage degradation and could serve as a promising cellular resource for OA treatment.

Background: The infrapatellar fat pad (IPFP) lies extrasynovial and intracapsular, preserving the joint cavity and serving as a biochemical regulator of inflammatory reactions. However, there is a lack of research on the relationship between anterior knee pain (AKP) and the IPFP after medial patellofemoral ligament reconstruction (MPFLR). Pinpointing the source of pain enables clinicians to promptly manage and intervene, facilitating personalized rehabilitation and improving patient prognosis. Methods: A total of 181 patients were included in the study. These patients were divided into the AKP group (n = 37) and the control group (n = 144). Clinical outcomes included three pain-related scores, Tegner activity score, patient satisfaction, etc. Imaging outcomes included the IPFP thickness, IPFP fibrosis, and the IPFP thickness change and preservation ratio. Multivariate analysis was used to determine the independent factors associated with AKP. Finally, the correlation between independent factors and three pain-related scores was analyzed to verify the results. Results: The control group had better postoperative pain-related scores and Tegner activity score than the AKP group (P < 0.01). The AKP group had lower IPFP thickness change ratio and preservation ratio (P < 0.001), and smaller IPFP thickness (P < 0.05). The multivariate analysis revealed that the IPFP thickness change ratio [OR = 0.895, P < 0.001] and the IPFP preservation ratio [OR = 0.389, P < 0.001] were independent factors related to AKP, with a significant correlation between these factors and pain-related scores [|r| > 0.50, P < 0.01]. Conclusions: This study showed the lower IPFP change ratio and preservation ratio may be independent factors associated with AKP after MPFLR. Early detection and targeted intervention of the underlying pain sources can pave the way for tailored rehabilitation programs and improved surgical outcomes. Level of evidence Level III: [ABSTRACT FROM AUTHOR]

The suprapatellar fat pad is an adipose tissue located in the anterior knee whose role in osteoarthritis is still debated. Considering that anatomy drives function, the aim of this histotopographic study was to investigate the specific morphological features of the suprapatellar fat pad versus the infrapatellar fat pad in the absence of osteoarthritis, for a broad comparative analysis. Suprapatellar fat pad and infrapatellar fat pad tissue samples (n = 10/group) underwent microscopical/immunohistochemical staining and transmission electron microscopy analysis; thus, tissue‐specific characteristics (i.e., vessels and nerve endings presence, lobuli, adipocytes features, septa), including extracellular matrix proteins prevalence (collagens, elastic fibers), were focused. Multiphoton microscopy was also adopted to evaluate collagen fiber orientation within the samples by Fast Fourier Transform (coherency calculation). The absence of inflammation was confirmed, and comparable counted vessels and nerve endings were shown. Like the infrapatellar fat pad, the suprapatellar fat pad appeared as a white adipose tissue with lobuli and septa of comparable diameter and thickness, respectively. Tissue main characteristics were also proved by both semithin sections and transmission electron microscopy analysis. The suprapatellar fat pad adipocytes were roundish and with a smaller area, perimeter, and major axis than that of the infrapatellar fat pad. The collagen fibers surrounding them showed no significant difference in collagen type I and significantly higher values for collagen type III in the infrapatellar fat pad group. Regarding the septa, elastic fiber content was statistically comparable between the two groups, even though more represented by the suprapatellar fat pad. Total collagen was significantly higher in the infrapatellar fat pad and comparing collagen type I and type III they were similarly represented in the whole cohort despite collagen type I appearing to be higher in the infrapatellar fat pad than in the suprapatellar fat pad and vice versa for collagen type III. Second harmonic generation microscopy confirmed through coherency calculation an anisotropic distribution of septa collagen fibers. From a mechanical point of view, the different morphological characteristics determined a major stiffness for the infrapatellar fat pad with respect to the suprapatellar fat pad. This study provides, for the first time, a topographic description of the suprapatellar fat pad compared to the infrapatellar fat pad; differences between the two groups may be attributed to a different anatomical location within the knee; the results gathered here may be useful for a more complete interpretation of osteoarthritis disease, involving not only cartilage but the whole joint. [ABSTRACT FROM AUTHOR]

Abstract Objectives 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. Methods 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. Results 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

Abstract Background Hoffa's fat pad is an intra-capsular extra-sinovial structure of the knee joint that has a significant biomechanical and metabolic role, minimizing the influence of stresses created by loading and generating cytokines. Changes in its size can lead to variations in the homeostasis of the knee in elderly patients. This work intends to assess the dimensional variations of Hoffa's fat pad associated to aging in both sexes, using MRI sagittal sequences acquired from the OAI (Osteoarthritis Initiative) database. Methods We examined the Hoffa's fat pad sagittal thickness in 217 men and women with knee osteoarthritis who were grouped into four age groups for the study: 40–49; 50–59; 60–69; and 70–80. 3T sagittal IW 2D TSE Fat-suppressed MRI sequences, taken from the OAI (Osteoarthritis Initiative) database, were examined. Results Hoffa’s fat pad thickness was shown to differ significantly between groups in both men and women, decreasing in the older individuals' groups (R = − 0.46; p 0.0001). By dividing the patients into ten-year age groups and by sex, the thickness of both the right knee and the left knee was examined. In fact, the average thickness of Hoffa's fat pad of the right knee was reported to be, in males, 33.6+/− 3 mm in subjects aged between 40 and 49 years, 31+/− 2.4 mm for patients aged between 50 and 59, 30.3 ± 1.8 mm in the group between 60 and 69 years and 28.7+/− 1.8 mm between 70 and 80 years. In women the values obtained were the following: 29+/− 1.6 mm between 40 and 49 years; 28.9+/− 2.6 mm in the group between 50 and 59 years, 25.3+/− 1.9 mm for patients aged 60 and 69 years and 26+/− 2 mm between 70 and 80 years. Similar results were obtained for the left knee. Conclusions Hoffa’s fat pad gradually thins with aging in both male and female patients with knee osteoarthritis, and this can be detected by evaluating the thickness of the fat pad on sagittal MRI sequences.

Background: Mesenchymal stem cell (MSC) therapy has ameliorative effects for treating knee osteoarthritis (KOA) disease. Moreover, there is a growing interest in using MSCs-derived secretome (Sec) containing trophic factors secreted by MSCs for KOA treatment. Recently, some studies have suggested that the combination of MSCs and Sec has the potential to treat the diseases. Aims: This study aimed to evaluate the ameliorative effects of combined administration of infrapatellar fat pad (IPFP)-derived MSCs, a type of adipose-derived stem cells (ASCs), for treating degenerated cartilage in a rat model of KOA. Methods: IPFP-ASCs were isolated from the IPFP of male rats. Sec was obtained from IPFP-ASCs in the fourth passage. Eight weeks after the induction of KOA by collagenase II, the rats were divided into 5 groups (n=5), including a control group with no treatment, and four experimental groups that received sodium hyaluronate (Hyalgan®, Hya), ASCs, Sec, and IPFP-ASCs+Sec, respectively by an infrapatellar injection. To perform the pathological and radiological evaluations, the animals were sacrificed 8 weeks later. Results: Our findings indicated that combined administration of the IPFP-ASCs and Sec statistically (P<0.05) improved scores of medial tibial and femoral condyles and medial fabella osteophytes. Also, it statistically (P<0.05) enhances the cartilage surface, matrix, cell distribution and population viability, and subchondral bone indices. No statistical difference was observed between IPFP-ASCs+Sec and IPFP-ASCs. Conclusion: Administration of IPFP-ASCs+Sec has a therapeutic potential to treat KOA in rats. However, there is no difference in the combined administration of IPFP-ASCs and Sec with IPFP-ASCs alone. [ABSTRACT FROM AUTHOR]

Objectives: 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. Methods: 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 fluidtreated MDMs were treated with platelet-rich plasma (PRP) and its effects on macrophage polarization were observed. Results: 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. Conclusion: 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. [ABSTRACT FROM AUTHOR]

Infrapatellar fat pad (IPFP) is closely associated with the development and progression of knee osteoarthritis (OA), but the underlying mechanism remains unclear. Here, it is find that IPFP from OA patients can secret small extracellular vesicles (sEVs) and deliver them into articular chondrocytes. Inhibition the release of endogenous osteoarthritic IPFP‐sEVs by GW4869 significantly alleviated IPFP‐sEVs‐induced cartilage destruction. Functional assays in vitro demonstrated that IPFP‐sEVs significantly promoted chondrocyte extracellular matrix (ECM) catabolism and induced cellular senescence. It is further demonstrated that IPFP‐sEVs induced ECM degradation in human and mice cartilage explants and aggravated the progression of experimental OA in mice. Mechanistically, highly enriched let‐7b‐5p and let‐7c‐5p in IPFP‐sEVs are essential to mediate detrimental effects by directly decreasing senescence negative regulator, lamin B receptor (LBR). Notably, intra‐articular injection of antagomirs inhibiting let‐7b‐5p and let‐7c‐5p in mice increased LBR expression, suppressed chondrocyte senescence and ameliorated the progression of experimental OA model. This study uncovers the function and mechanism of the IPFP‐sEVs in the progression of OA. Targeting IPFP‐sEVs cargoes of let‐7b‐5p and let‐7c‐5p can provide a potential strategy for OA therapy. [ABSTRACT FROM AUTHOR]

Diabetes mellitus (DM) has been suggested as a potential risk factor for knee osteoarthritis (KOA), and its underlying mechanisms remain unclear. The infrapatellar fat pad (IPFP) contributes to OA through inflammatory mediator secretion. Mast cells' (MCs) role in diabetic IPFP pathology is unclear. In 156 KOA patients, hemoglobin A1c (HbA1c) was stratified (HbA1c ≥ 6.5, n = 28; HbA1c < 6.5, n = 128). MC markers (TPSB2, CPA3) in IPFP were studied. Propensity-matched cohorts (n = 27 each) addressed demographic differences. MC-rich fraction (MC-RF) and MC-poor fraction (MC-PF) were isolated, comparing MC markers and genes elevated in diabetic skin-derived MC (PAXIP1, ARG1, HAS1, IL3RA). TPSB2 and CPA3 expression were significantly higher in HbA1c ≥ 6.5 vs. <6.5, both before and after matching. MC-RF showed higher TPSB2 and CPA3 expression than MC-PF in both groups. In the HbA1c ≥ 6.5 group, PAXIP1 and ARG1 expression were significantly higher in the MC-RF than MC-PF. However, no statistical difference in the evaluated genes was detected between the High and Normal groups in the MC-RF. Elevated TPSB2 and CPA3 levels in the IPFP of high HbA1c patients likely reflect higher numbers of MCs in the IPFP, though no difference was found in MC-specific markers on a cell-to-cell basis, as shown in the MC-RF comparison. These findings deepen our understanding of the intricate interplay between diabetes and KOA, guiding targeted therapeutic interventions. [ABSTRACT FROM AUTHOR]

Purpose: Mesenchymal stem cells/medicinal signaling cells (MSCs) possess therapeutic potential and are used in regenerative orthopaedics. The infra-patellar fat pad (IFP) is partially resected during knee arthroscopy (KASC) and contains MSCs. Heat, irrigation, and mechanical stress during KASC may decrease MSC's therapeutic potential. This study assessed MSCs' regenerative potential after arthroscopic IFP harvest and potential effects of two blood products (BP) (platelet-rich plasma (PRP), hyperacute serum (HAS)) on MSCs' viability and chondrogenic differentiation capacity. Methods: IFP was arthroscopically harvested, isolated, and counted (n = 5). Flow cytometry was used to assess cell viability via staining with annexin V/7-AAD and stemness markers via staining for CD90, CD73, and CD105. MSCs were incubated with blood products, and metabolic activity was determined via an XTT assay. Deposition of cartilage extracellular matrix was determined in histologic sections of chondrogenically differentiated 3D pellet cultures via staining with Alcian Blue. Expression of cartilage-specific genes (SOX9, MMP3/13, ACAN, COL1/2) was analyzed via quantitative PCR. Results: MSC isolation from IFP yielded 2.66*106 ± 1.49*106 viable cells from 2.7 (0.748) g of tissue. MSC markers (CD 90/105/73) were successfully detected and annexin V staining showed 81.5% viable cells. XTT showed increased metabolic activity. Within the BP groups, this increase was significant (days 0–14, p < 0.05). PCR showed expression of cartilage-specific genes in each group. COL2 (p < 0.01) as well as ACAN (p < 0.001) expression levels were significantly higher in the HAS group. Histology showed successful differentiation. Conclusion: Arthroscopic harvest of IFP-MSCs yields sufficient cells with maintained regenerative potential and viability. Blood products further enhance MSCs' viability. [ABSTRACT FROM AUTHOR]

Objective: To 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). Methods: We 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. Results: Univariate 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). Conclusion: Our 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.

Background: Dedifferentiated fat cells (DFATs) are highly homogeneous and multipotent compared with adipose-derived stromal cells (SCs). Infrapatellar fat pad (IFP)–SCs have advanced chondrogenic potency; however, whether IFP-DFATs could serve as better cell material remains unclear. Here, we aimed to examine the influence of age and body mass index (BMI) on the features of IFPs and IFP-derived cells (IFP–SCs and IFP-DFATs) with exploration of the clinical utilization of IFP-DFATs. Methods: We collected IFPs with isolation of paired IFP-SCs and IFP-DFATs from individuals aged 65 years and older with distinct body weights who underwent total knee replacement for osteoarthritis (OA). Flow cytometry was used to characterize the cellular immunophenotypes. Adipogenesis and chondrogenesis were performed in vitro. Real-time qPCR, western blotting, and Oil Red O or Alcian blue staining were performed to evaluate inflammation, adipogenesis, and chondrogenesis. RNA sequencing and Seahorse analyses were conducted to explore the underlying mechanisms. Results: We found that IFPs from old or normal-weight individuals with knee OA were pro-inflammatory, and that interleukin-6 (IL-6) signaling was associated with multiple immune-related molecules, whereas IFP-derived cells could escape the inflammatory properties. Aging plays an important role in diminishing the chondrogenic and adipogenic abilities of IFP-SCs; however, this effect was avoided in IFP-DFATs. Generally, IFP-DFATs presented a steady state of chondrogenesis (less influenced by age) and consistently enhanced adipogenesis compared to paired IFP-SCs in different age or BMI groups. RNA sequencing and Seahorse analysis suggested that the downregulation of eukaryotic initiation factor 2 (EIF2) signaling and enhanced mitochondrial function may contribute to the improved cellular biology of IFP-DFATs. Conclusions: Our data indicate that IFP-DFATs are superior cell material compared to IFP-SCs for cartilage differentiation and adipogenesis, particularly in advanced aging patients with knee OA. The translational potential of this article: These results provide a novel concept and supportive evidence for the use of IFP-DFATs for cell therapy or tissue engineering in patients with knee OA. Using Ingenuity Pathway Analysis (IPA) of RNA-seq data and Seahorse analysis of mitochondrial metabolic parameters, we highlighted that some molecules, signaling pathways, and mitochondrial functions are likely to be jointly coordinated to determine the enhanced biological function in IFP-DFATs.

Abstract Infrapatellar fat pad (IPFP) is closely associated with the development and progression of knee osteoarthritis (OA), but the underlying mechanism remains unclear. Here, it is find that IPFP from OA patients can secret small extracellular vesicles (sEVs) and deliver them into articular chondrocytes. Inhibition the release of endogenous osteoarthritic IPFP‐sEVs by GW4869 significantly alleviated IPFP‐sEVs‐induced cartilage destruction. Functional assays in vitro demonstrated that IPFP‐sEVs significantly promoted chondrocyte extracellular matrix (ECM) catabolism and induced cellular senescence. It is further demonstrated that IPFP‐sEVs induced ECM degradation in human and mice cartilage explants and aggravated the progression of experimental OA in mice. Mechanistically, highly enriched let‐7b‐5p and let‐7c‐5p in IPFP‐sEVs are essential to mediate detrimental effects by directly decreasing senescence negative regulator, lamin B receptor (LBR). Notably, intra‐articular injection of antagomirs inhibiting let‐7b‐5p and let‐7c‐5p in mice increased LBR expression, suppressed chondrocyte senescence and ameliorated the progression of experimental OA model. This study uncovers the function and mechanism of the IPFP‐sEVs in the progression of OA. Targeting IPFP‐sEVs cargoes of let‐7b‐5p and let‐7c‐5p can provide a potential strategy for OA therapy.

Background: To study the functional outcome of surgical management in Hoffa's disease. Methods: This prospective study was conducted in the Department of Orthopaedics in a tertiary health care centre between 1st January 2020 and 31st December 2021. A total of three patients (2 males and 1 female) with Hoffa's disease were included in the study. Results: "Tegner-Lysholm score" was used for evaluation of function, and the mean Tegner–Lysholm score was 93. All the three patients had normal range of motion at 1 year follow-up. Conclusion: Hoffa's disease has low incidence, and hence diagnosing the condition correctly is of utmost importance for its proper management. [ABSTRACT FROM AUTHOR]

Fibrosis of the infrapatellar fat pad (IFP) occurs after knee joint surgery or during knee osteoarthritis (KOA) and causes persistent pain and limited mobility. Previous studies demonstrated that treating IFP fibrosis alleviated pain in animal models. In this study, we examined the effects of hyaluronic acid (HA) sheet transplantation on IFP fibrosis and articular cartilage degeneration in a monoiodoacetic acid (MIA) rat arthritis model (95 male rats). Rats received bilateral intra‐articular MIA injections (1.0 mg/30 μL) and underwent surgery 4 days later. HA sheets were transplanted on the right knee of each rat (HA group), with the left knee receiving sham surgery (sham group). Incapacitance tests were performed at multiple time points up to 28 days after MIA injection. Macroscopic, histological, and immunohistochemical analyzes were performed 14 and 28 days after injection. The concentrations of HA and interleukin‐1β (IL‐1β) in the synovial fluid were measured using ELISA. Transplantation of HA sheets could alleviate persistent pain 10–28 days after injection. The HA sheets inhibited articular cartilage degeneration at 14 days. Fibrosis and the invasion of calcitonin gene‐related peptide‐positive nerve fiber endings in the IFP were inhibited at both 14 and 28 days. Moreover, the HA sheets remained histologically until 10 days after transplantation. The concentration of HA reached its peak on Day 10 after transplantation; the concentration of IL‐1β in the sham group was significantly higher than that in the HA group on Day 7. Therefore, HA sheets could be a promising option to treat IFP fibrosis occurring in KOA and after knee joint surgery. [ABSTRACT FROM AUTHOR]

Abstract Background The infrapatellar fat pad (IFP) may have bilateral influence on knee osteoarthritis (KOA). IFP evaluation may be a key contributor to the diagnostic and clinical management of KOA. Few studies have evaluated KOA-related IFP alteration with radiomics. We investigated radiomic signature for the assessment of IFP for KOA progression in older adults. Methods A total of 164 knees were enrolled and grouped based on Kellgren-Lawrence (KL) scoring. MRI-based radiomic features were calculated from IFP segmentation. The radiomic signature was developed using the most predictive subset of features and the machine-learning algorithm with minimum relative standard deviation. KOA severity and structure abnormality were assessed using a modified whole-organ magnetic resonance imaging score (WORMS). The performance of the radiomic signature was evaluated and the correlation with WORMS assessments was analyzed. Results The area under the curve of the radiomic signature for diagnosing KOA was 0.83 and 0.78 in the training and test datasets, respectively. Rad-scores were 0.41 and 2.01 for the training dataset in the groups with and without KOA (P

The knowledge of osteoarthritis (OA) has nowadays been extended from a focalized cartilage disorder to a multifactorial disease. Although recent investigations have reported that infrapatellar fat pad (IPFP) can trigger inflammation in the knee joint, the mechanisms behind the role of IPFP on knee OA progression remain to be defined. Here, dysregulated osteopontin (OPN) and integrin β3 signaling are found in the OA specimens of both human and mice. It is further demonstrated that IPFP‐derived OPN participates in OA progression, including activated matrix metallopeptidase 9 in chondrocyte hypertrophy and integrin β3 in IPFP fibrosis. Motivated by these findings, an injectable nanogel is fabricated to provide sustained release of siRNA Cd61 (RGD−Nanogel/siRNA Cd61) that targets integrins. The RGD−Nanogel possesses excellent biocompatibility and desired targeting abilities both in vitro and in vivo. Local injection of RGD−Nanogel/siRNA Cd61 robustly alleviates the cartilage degeneration, suppresses the advancement of tidemark, and reduces the subchondral trabecular bone mass in OA mice. Taken together, this study provides an avenue for developing RGD−Nanogel/siRNA Cd61 therapy to mitigate OA progression via blocking OPN‐integrin β3 signaling in IPFP. [ABSTRACT FROM AUTHOR]

Infrapatellar fat pad (IPFP) proton density–weighted images (PdWI) hyperintense regions on MRI are an important imaging feature of knee osteoarthritis (KOA) and are thought to represent inflammation which may induce knee pain. The aim of the study was to compare the intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI) findings of PdWI hyperintense regions of IPFP between symptomatic and asymptomatic KOA and to determine whether IVIM-DWI parameters can be used as an objective biomarker for symptomatic KOA. In total, 84 patients with symptomatic KOA, 43 asymptomatic KOA persons, and 30 healthy controls with MRI were retrospectively reviewed. Demographic, IPFP-synovitis, Western Ontario and McMaster Osteoarthritis Index (WOMAC) pain sub-score, IPFP volume and depth and quantitative parameters of IVIM-DWI were collected. The chi-square test, Binary logistic regression and receiver operating characteristic curve (ROC) analysis were used for diagnostic performance comparison. The IPFP volume and depth were statistically significant differences between the non-KOA and sKOA groups (p <0.05). The IPFP PdWI hyperintense regions demonstrated significantly higher values of D and D* in the symptomatic KOA compared to those in the asymptomatic KOA (1.51±0.47 vs. 1.73±0.40 for D and 19.24±6.44 vs. 27.09±9.75 for D*) (both p <0.05). Multivariate logistic regression analyses showed that Higher D and D* values of IPFP hyperintense region were significantly associated with higher risks of knee pain (OR: 1.97; 95% CI: 1.21-3.19; p =0.006 for D and OR: 1.24; 95% CI: 1.09-1.41; p =0.001 for D*). Sensitivity and specificity of D value for symptomatic KOA were 80.28% and 83.33%, with an AUC of 0.78 (0.68-0.86). D* value had the sensitivity with 92.96% and a specificity of 58.33%, with an AUC of 0.82 (0.73-0.89) for symptomatic KOA. IVIM-DWI can be used as an additional functional imaging technique to study IPFP with signal abnormalities on PdWI, and the D and D* values may have potential value to predict the symptom in mild-to-moderate KOA patients. [ABSTRACT FROM AUTHOR]

Abstract Background Interpretation of patellar ligament (PL) ultrasonography may be difficult, as hypoechoic or heterogenous echogenicity are common findings. Verifying suspected disease of equine PLs by histopathology is also problematic as descriptions of normal PL vascularity and histology are scarce. The current study describes the PL and infrapatellar fat pad (IFP) vascular pattern from computed tomography scans of barium perfused normal equine specimens (n = 8; age 10 days to 18 years), as well as routine histology to serve as a reference for future investigations into PL pathology and IFP disease. Results The PLs received a bipolar blood supply. Vascular architecture consisted of numerous distinct longitudinal vessels with several horizontal connections, which branched into extensive latticeworks of smaller vessels throughout the ligaments. Several vascular connections between the PLs and the IFP were identified. One distinct longitudinal vessel was seen entering each of the IFP lobes at the distocranial aspect, branching extensively into lobar vascular networks which anastomosed by several horizontal branches at the mid portion of the IFP where the two lobes merge. Histologically, there were large variations in PL interfascicular endotenon thickness, vascularity and fatty infiltration; these parameters increased with age for the intermediate and medial PL. Areas of metaplastic tenocytes / chondroid metaplasia were identified in all investigated adult medial PLs; in 2/7 in the intermediate PL and in 4/7 in the lateral PL. The adult IFP consisted of white unilocular adipose tissue, organized in lobules separated by thin connective tissue septa increasing in thickness towards the periphery and the distocentral aspect. Conclusions The equine PLs and IFP are highly vascularized structures with ample vascular connections suggestive of crosstalk. This, together with the large variation in PL endotenon thickness, vascularity and fatty infiltration, should be taken into consideration when assessing potential PL histopathology as these changes increase with age and are found in horses without clinical signs of stifle disease. Metaplastic tenocytes / chondroid metaplasia should be considered a normal finding throughout the medial PL and is not age dependent. The role of the equine IFP in stifle disease has yet to be elucidated.

Abstract Background Knee osteoarthritis (OA) is a prevalent disabling disorder that involves changes in articular cartilage damage, subchondral bone remodeling, synovitis, and abnormal infrapatellar fat pad (IPFP). Due to the complicated etiology and numerous phenotypes of knee OA, limited improvement is achieved for treatments among knee OA patients with different phenotypes. Inflammatory OA phenotype is a typical knee OA phenotype, and individualized treatment targeting inflammation is a promising way to obtain an optimal therapeutic effect for people with inflammatory knee OA phenotype. Glucocorticoid is a traditional anti-inflammatory drug for knee OA, and intra-articular glucocorticoid injections are recommended clinically. However, emerging evidence has shown that repeated intra-articular glucocorticoid injections in the long term would induce cartilage loss. IPFP and its adjacent synovium are considered as the main source of inflammation in knee OA. This GLITTERS trial aims to investigate if a glucocorticoid injection into the IPFP is effective and safe over 12 weeks among knee OA patients with an inflammatory phenotype. Methods GLITTERS is a multicenter, double-blinded, randomized, and placebo-controlled clinical trial among knee OA patients with both Hoffa-synovitis and effusion-synovitis. Sixty participants will be allocated randomly and equally to either the glucocorticoid group or the control group. Each group will receive an injection of glucocorticoid or saline into the IPFP with an intra-articular hyaluronic acid injection as a background treatment at baseline and be followed at 4, 8, and 12 weeks. The primary outcomes will be changes in knee pain on a visual analog scale and effusion-synovitis volume measured on magnetic resonance imaging (MRI). The secondary outcomes will be changes in the total score of Western Ontario and McMaster Universities Osteoarthritis Index score, MRI-detected Hoffa-synovitis score, quality of life, pain medication use, IPFP volume, and the incidence of adverse reactions. Data analyses based on the intention-to-treat principle will include mixed-effects regressions, Wilcoxon rank-sum tests, and chi-square tests (or Fisher’s exact test). Discussion GLITTERS may provide high-quality evidence for the efficacy and safety of ultrasound-guided glucocorticoid injections into IPFP among people with inflammatory knee OA in a short term. The results of this trial are expected to provide a reliable reference for a longer-term risk–benefit profile of this treatment in the future. Trial registration ClinicalTrials.gov NCT05291650. Registered on 23 March 2022.

Introduction: Infrapatellar fat pad (IFP)-derived mesenchymal stem cells (MSCs) have high chondrogenic potential and are attractive cell sources for cartilage regeneration. During ceiling culture to acquire the characteristics of MSCs, mature adipocytes from fat tissue are known to undergo dedifferentiation, generating dedifferentiated fat (DFAT) cells. The purpose of the present study was to compare the yields and biological properties of IFP-derived MSCs and IFP-derived DFAT cells. Methods: IFPs were harvested from the knees of 8 osteoarthritis (OA) patients. DFAT cells were obtained using a ceiling culture of adipocytes isolated from the floating top layer of IFP digestion. MSCs were obtained by culturing precipitated stromal vascular fraction cells. We compared the P0 cell yields, surface antigen profile, colony formation ability, and multipotency of DFAT cells and MSCs. Results: The P0 cell yields per flask and the estimated total cell yields from 1 g of IFP were much greater for MSCs than for DFAT cells. Both MSCs and DFAT cells were positive for MSC markers. No obvious difference was observed in colony formation ability. In differentiation assays, DFAT cells produced greater amounts of lipid droplets, calcified tissue, and glycosaminoglycan than MSCs did. Adipogenic and chondrogenic gene expressions were upregulated in DFAT cells. Conclusions: IFP-derived DFAT cells showed higher adipogenic and chondrogenic potentials than IFP-derived MSCs, but they had a poor cell yield.

Abstract Background The anterior knee compartment is filled by the infrapatellar fat pad (IFP) and has been emphasized as a source of anterior knee pain (AKP). Case presentation A 51-year-old woman sustained a right tibial plateau and open diaphyseal fracture 2 years earlier. She remained with chronic AKP after undergoing bone fixations. Increased anterior portion of the IFP brightness and decreased adipose tissue gliding with flexion and extension compared to the unaffected side was shown on ultrasonography. An injection of 0.2% lidocaine between the patellar tendon and IFP, and into the IFP under ultrasound guidance, immediately relieved the pain. The pain kept recurring although injections were effective for a while; thus, surgery was scheduled. Scar tissue on the IFP surface was endoscopically excised and her pain dramatically reduced. Conclusion This is the first report in which the detection of increased brightness on ultrasound of IFP and the injections into the IFP triggered an additional surgical intervention. Ultrasound evaluation and injection may be beneficial in pain clinic patients presenting with AKP and may provide an opportunity for diagnosis.

Purpose: The management of infrapatellar fat pad (IPFP) during total knee arthroplasty (TKA) is the subject of ongoing debate. There is conflicting evidence whether IPFP should be preserved or resected during TKA to improve clinical outcomes. This study sought to establish if there is a benefit of one over another in terms of clinical function & patient satisfaction. Material & Methods: Total of 67 patients (96 knees), 11 males & 56 females with a mean age of 66.29 years, who underwent TKA between 2016 and 2020 were included in the study. The planning for IPFP preservation (IPFP-P) on right side (50 knees) & IPFP resection (IPFP-R) on left side (46 knees) was done prospectively. We prospectively evaluated clinical outcomes post-TKA, comparing the right knee to the left knee in terms of IPFP-P vs IPFP-R using the oxford knee scoring (OKS) system. The SF-12 was used to evaluate and compare patient satisfaction between the two groups. Results: The mean OKS in the IPFP-P group was 42.86 ± 2.63 & in the IPFP-R group was 44.22 ± 2.40. The OKS differed significantly between the two groups (p < 0.05). Patient with IPFP-R group had significantly better OKS. The mean Sf-12 (physical & mental component) in the IPFP-P was 51.05 ± 4.15 & 59.29 ± 2.53 & in IPFP-R was 51.23 ± 4.74 & 59.24 ± 2.78, showing no significant differences. Conclusion: Our study shows that IPFP-R gave marginally better patient-reported functional outcome scores (OKS), but there was no difference in patient satisfaction (SF-12 scores) between the two groups. [ABSTRACT FROM AUTHOR]

Background: The infrapatellar fat pad (IFP) may have bilateral influence on knee osteoarthritis (KOA). IFP evaluation may be a key contributor to the diagnostic and clinical management of KOA. Few studies have evaluated KOA-related IFP alteration with radiomics. We investigated radiomic signature for the assessment of IFP for KOA progression in older adults. Methods: A total of 164 knees were enrolled and grouped based on Kellgren-Lawrence (KL) scoring. MRI-based radiomic features were calculated from IFP segmentation. The radiomic signature was developed using the most predictive subset of features and the machine-learning algorithm with minimum relative standard deviation. KOA severity and structure abnormality were assessed using a modified whole-organ magnetic resonance imaging score (WORMS). The performance of the radiomic signature was evaluated and the correlation with WORMS assessments was analyzed. Results: The area under the curve of the radiomic signature for diagnosing KOA was 0.83 and 0.78 in the training and test datasets, respectively. Rad-scores were 0.41 and 2.01 for the training dataset in the groups with and without KOA (P < 0.001) and 0.63 and 2.31 for the test dataset (P = 0.005), respectively. WORMS significantly and positively correlated with rad-scores. Conclusions: The radiomic signature may be a reliable biomarker to detect IFP abnormality of KOA. Radiomic alterations in IFP were associated with severity and knee structural abnormalities of KOA in older adults. [ABSTRACT FROM AUTHOR]

Purpose: Anterior knee pain (AKP) may occur after anterior cruciate ligament (ACL) reconstruction. The present study investigated the relationship between the change in infrapatellar fat pad (IFP) thickness assessed using ultrasonography (US) and AKP on squatting in patients after ACL reconstruction. Methods: Patients were enrolled 3 months after ACL reconstruction using the bone-tendon-bone (BTB) technique. Subjects were divided into the AKP group (numerical rating scale [NRS] score ≥ 1) and control group (NRS score < 1) using a NRS of pain on squatting, and intergroup comparisons were performed. On US evaluation, measurement angles of the knee joint were 0° and 30° in the supine position. The IFP between the femoral intercondylar notch and patellar tendon was measured on short-axis images. The changes in IFP thickness were calculated from values measured at different angles of the knee joint. Results: Twenty-one patients (mean age 24.9 ± 9.3 years) were included in the present study: 12 in the AKP group (9 males, 3 females) and nine in the control group (5 males, 4 females). A significant difference in the change in IFP thickness at 3 months was observed between the AKP and control groups (0.67 ± 0.44 mm vs. 1.84 ± 0.34 mm, p < 0.001). There was a negative correlation between the change in IFP thickness and the NRS score (r = − 0.720, p < 0.001) in reconstructed knees. Conclusion: A smaller change in IFP thickness assessed using US after ACL reconstruction was identified as a factor contributing to AKP on squatting. [ABSTRACT FROM AUTHOR]

Background: Infrapatellar fat pad (IFP) fibrosis is reportedly associated with anterior knee pain and the progression of patellofemoral osteoarthritis after anterior cruciate ligament reconstruction (ACLR). However, causes of IFP fibrosis after ACLR have not been sufficiently investigated. Purpose: To compare the descriptive characteristics, clinical outcomes, and inflammatory cytokine levels in the synovial fluid between patients who underwent ACLR with versus without severe IFP fibrosis. Study Design: Cohort study; Level of evidence, 3. Methods: Patients who underwent primary ACLR using autologous hamstring tendon were divided into 2 groups based on magnetic resonance imaging IFP fibrosis scoring (grades 0-5) at 3 months after surgery: the severe fibrosis group (grades 4 and 5) and mild fibrosis group (grades 0-3). Synovial fluid was aspirated on postoperative day 3 or 4 to measure inflammatory cytokine levels. Patient characteristics, clinical outcomes at 3 and 12 months after surgery, and inflammatory cytokine (interleukin [IL]-1β, IL-2, IL-6, IL-8, IL-10, tumor necrosis factor–α, and interferon-γ) levels were compared between the groups. Results: Of the 36 patients included, 7 were allocated to the severe fibrosis group and 29 were allocated to the mild fibrosis group. The severe fibrosis group had a significantly longer operation time (153.0 vs 116.5 minutes for mild fibrosis; P =.007). Compared with the mild fibrosis group, the severe fibrosis group had greater pain during stair climbing (2.0 vs 0.7; P =.01) and a lower extension muscle strength ratio (operated/healthy side, 52.9% vs 76.1%; P <.001) at 3 months, and the severe fibrosis group had a lower Lysholm score (93.7 vs 97.3; P =.026) and greater knee extension (0.3° vs 1.9°; P =.043) and flexion angle restriction (142.9° vs 149.0°; P =.013) at 12 months. The severe fibrosis group demonstrated higher IL-1β (2.6 vs 1.4 pg/mL; P =.022), IL-6 (2.0 vs 1.1 ng/mL; P =.029), and interferon-γ levels (11.3 vs 4.0 pg/mL; P =.044). Conclusion: Severe IFP fibrosis was associated with a longer operation time, higher inflammatory cytokine level in the synovial fluid, and worse clinical outcomes at 3 and 12 months after ACLR. [ABSTRACT FROM AUTHOR]

Abstract The knowledge of osteoarthritis (OA) has nowadays been extended from a focalized cartilage disorder to a multifactorial disease. Although recent investigations have reported that infrapatellar fat pad (IPFP) can trigger inflammation in the knee joint, the mechanisms behind the role of IPFP on knee OA progression remain to be defined. Here, dysregulated osteopontin (OPN) and integrin β3 signaling are found in the OA specimens of both human and mice. It is further demonstrated that IPFP‐derived OPN participates in OA progression, including activated matrix metallopeptidase 9 in chondrocyte hypertrophy and integrin β3 in IPFP fibrosis. Motivated by these findings, an injectable nanogel is fabricated to provide sustained release of siRNA Cd61 (RGD−Nanogel/siRNA Cd61) that targets integrins. The RGD−Nanogel possesses excellent biocompatibility and desired targeting abilities both in vitro and in vivo. Local injection of RGD−Nanogel/siRNA Cd61 robustly alleviates the cartilage degeneration, suppresses the advancement of tidemark, and reduces the subchondral trabecular bone mass in OA mice. Taken together, this study provides an avenue for developing RGD−Nanogel/siRNA Cd61 therapy to mitigate OA progression via blocking OPN‐integrin β3 signaling in IPFP.

Objective To investigate the feasibility of measuring the thickness of adult subpatellar fat pad based on MRI and the correlation between the thickness of adult subpatellar fat pad and sex, age, weight and height, to provide the basis for keeping the thickness of subpatellar fat pad in total knee arthroplasty. Methods 1 019 cases of 18-80-year-old adult knee MRI scan images were randomly selected as the research object, and the median sagittal image of the knee joint was taken as the measurement plane. The distance of the farthest point of the edge was used as the measurement thickness, the measurement results were statistically analyzed by SPSS26.0 statistical software package, the measurement data of normal distribution were expressed by, and the comparison of measurement data of normal distribution between two groups was used two independent samples t Pearson correlation analysis was used for correlation analysis, and P < 0.05 indicated that the difference was statistically significant. Results The average thickness of the infrapatellar fat pad in males was greater than that in females, which were (28.08±4.64) mm and (24.58±4.22) mm, respectively, and the difference was statistically significant (P < 0.05). The ages of males and females were (49.09±17.78) years old, respectively. and (50.42±17.88) years old, the difference was not statistically significant (P > 0.05); the height and weight of males were greater than those of females, and the difference was statistically significant (P < 0.05), which was considered as a physiological difference; male infrapatellar fat pad There was no correlation between the thickness and age, height and weight (P > 0.05); the thickness of the infrapatellar fat pad in women was correlated with body weight (P < 0.05), but not with age and height (P > 0.05). Conclusion The average thickness of subpatellar fat pad in male is larger than that in female and has no correlation with age, height and weight. [ABSTRACT FROM AUTHOR]

Background: Interpretation of patellar ligament (PL) ultrasonography may be difficult, as hypoechoic or heterogenous echogenicity are common findings. Verifying suspected disease of equine PLs by histopathology is also problematic as descriptions of normal PL vascularity and histology are scarce. The current study describes the PL and infrapatellar fat pad (IFP) vascular pattern from computed tomography scans of barium perfused normal equine specimens (n = 8; age 10 days to 18 years), as well as routine histology to serve as a reference for future investigations into PL pathology and IFP disease. Results: The PLs received a bipolar blood supply. Vascular architecture consisted of numerous distinct longitudinal vessels with several horizontal connections, which branched into extensive latticeworks of smaller vessels throughout the ligaments. Several vascular connections between the PLs and the IFP were identified. One distinct longitudinal vessel was seen entering each of the IFP lobes at the distocranial aspect, branching extensively into lobar vascular networks which anastomosed by several horizontal branches at the mid portion of the IFP where the two lobes merge. Histologically, there were large variations in PL interfascicular endotenon thickness, vascularity and fatty infiltration; these parameters increased with age for the intermediate and medial PL. Areas of metaplastic tenocytes / chondroid metaplasia were identified in all investigated adult medial PLs; in 2/7 in the intermediate PL and in 4/7 in the lateral PL. The adult IFP consisted of white unilocular adipose tissue, organized in lobules separated by thin connective tissue septa increasing in thickness towards the periphery and the distocentral aspect. Conclusions: The equine PLs and IFP are highly vascularized structures with ample vascular connections suggestive of crosstalk. This, together with the large variation in PL endotenon thickness, vascularity and fatty infiltration, should be taken into consideration when assessing potential PL histopathology as these changes increase with age and are found in horses without clinical signs of stifle disease. Metaplastic tenocytes / chondroid metaplasia should be considered a normal finding throughout the medial PL and is not age dependent. The role of the equine IFP in stifle disease has yet to be elucidated. [ABSTRACT FROM AUTHOR]

Background: Knee osteoarthritis (OA) is a prevalent disabling disorder that involves changes in articular cartilage damage, subchondral bone remodeling, synovitis, and abnormal infrapatellar fat pad (IPFP). Due to the complicated etiology and numerous phenotypes of knee OA, limited improvement is achieved for treatments among knee OA patients with different phenotypes. Inflammatory OA phenotype is a typical knee OA phenotype, and individualized treatment targeting inflammation is a promising way to obtain an optimal therapeutic effect for people with inflammatory knee OA phenotype. Glucocorticoid is a traditional anti-inflammatory drug for knee OA, and intra-articular glucocorticoid injections are recommended clinically. However, emerging evidence has shown that repeated intra-articular glucocorticoid injections in the long term would induce cartilage loss. IPFP and its adjacent synovium are considered as the main source of inflammation in knee OA. This GLITTERS trial aims to investigate if a glucocorticoid injection into the IPFP is effective and safe over 12 weeks among knee OA patients with an inflammatory phenotype. Methods: GLITTERS is a multicenter, double-blinded, randomized, and placebo-controlled clinical trial among knee OA patients with both Hoffa-synovitis and effusion-synovitis. Sixty participants will be allocated randomly and equally to either the glucocorticoid group or the control group. Each group will receive an injection of glucocorticoid or saline into the IPFP with an intra-articular hyaluronic acid injection as a background treatment at baseline and be followed at 4, 8, and 12 weeks. The primary outcomes will be changes in knee pain on a visual analog scale and effusion-synovitis volume measured on magnetic resonance imaging (MRI). The secondary outcomes will be changes in the total score of Western Ontario and McMaster Universities Osteoarthritis Index score, MRI-detected Hoffa-synovitis score, quality of life, pain medication use, IPFP volume, and the incidence of adverse reactions. Data analyses based on the intention-to-treat principle will include mixed-effects regressions, Wilcoxon rank-sum tests, and chi-square tests (or Fisher's exact test). Discussion: GLITTERS may provide high-quality evidence for the efficacy and safety of ultrasound-guided glucocorticoid injections into IPFP among people with inflammatory knee OA in a short term. The results of this trial are expected to provide a reliable reference for a longer-term risk–benefit profile of this treatment in the future. Trial registration: ClinicalTrials.gov NCT05291650. Registered on 23 March 2022. [ABSTRACT FROM AUTHOR]

Objective To explore the longitudinal association of quantitative infrapatellar fat pad (IPFP) signal intensity alteration with OA-related biomarkers. Methods Eighteen OA-related biochemical biomarkers of 600 knee OA participants in the Foundation for the National Institutes of Health OA Biomarkers Consortium (FNIH) study were extracted. The quantitative IPFP signal intensity measures were acquired based on magnetic resonance imaging, including mean value [Mean (IPFP)] and standard deviation [sDev (IPFP)] of the whole IPFP signal intensity, median value [Median (H)] and upper quartile value [UQ (H)] of high signal intensity, the ratio of volume of high signal intensity to volume of whole IPFP signal intensity [Percentage (H)] and Clustering factor (H). The linear mixed-effect model was applied to determine the longitudinal associations between IPFP signal intensity alteration and biochemical biomarkers over 2 years. Results All IPFP measures except for Clustering factor (H) were positively associated with urine collagenase-cleaved type II collagen neoepitope (uC2C), urine C-terminal cross-linked telopeptide of type II collagen (uCTX-II), urine C-terminal cross-linked telopeptide of type I collagen-α (uCTX-Iα) and urine N-terminal cross-linked telopeptide of type I collagen (uNTX-I). Mean (IPFP), Median (H) and Percentage (H) were positively associated with the nitrated form of an epitope located in the triple helix of type II collagen (Coll2-1 NO2). Mean (IPFP), Median (H) and UQ (H) were positively associated with sCTX-I and uCTX-Iβ. Positive associations between sDev (IPFP), Percentage (H) and serum hyaluronic acid (sHA) were found. Conclusion Our results suggest a role of IPFP signal intensity alteration in joint tissue remodelling on a molecular level. [ABSTRACT FROM AUTHOR]

Osteoarthritis (OA) is a progressive degenerative disease resulting in joint deterioration. It is a whole organ disease characterized by cartilage degeneration and varying degrees of synovitis, involving pathological changes in all joint tissues, such as cartilage, subchondral bone, ligaments, meniscus, synovium, and infrapatellar fat pad (IPFP). IPFP is the largest adipose tissue structure in the knee joint and is composed of fat cells, immune cells and blood vessels. Moreover, IPFP is located close to the cartilage and bone surface so that it may reduce the impact of loading and absorb forces generated through the knee joint, and may have a protective role in joint health. IPFP has been shown to release various cytokines and adipokines that play pro-inflammatory and pro-catabolic roles in cartilage, promoting OA progression. Intra-articular injections of IPFP-derived mesenchymal stem cells and exosomes have been shown to reduce pain and prevent OA progression in patients with knee OA. Previous studies have shown that IPFP has a biphasic effect on OA progression. This article reviews the latest research progress of IPFP, discusses the role and mechanism of IPFP in OA, provide new intervention strategies for the treatment of OA. This article will also discuss the handling of IPFP during the procedure of total knee arthroplasty. [Display omitted] • IPFP is the largest adipose tissue in the knee, and IPFP quality has been implicated as a marker to predicate knee OA. • IPFP can release inflammatory factors and adipokines, which participate in the pathophysiology of knee OA. • IPFP-MSCs have emerged a promising cell source for cartilage repair. However, the application of MSCs has been controversial. • Single-cell transcriptomic approaches demonstrate the presence of significant cellular heterogeneity in the IPFP. • Due to the biphasic nature of IPFP in OA, the decision to remove the IPFP at surgery should be treated with caution. [ABSTRACT FROM AUTHOR]

Introduction: Mature adipocyte-derived dedifferentiated fat cells (DFATs) are mesenchymal stem cell (MSC)-like cells with high proliferative ability and multilineage differentiation potential. In this study, we first examined whether DFATs can be prepared from infrapatellar fat pad (IFP) and then compared phenotypic and functional properties of IFP-derived DFATs (IFP-DFATs) with those of subcutaneous adipose tissue (SC)-derived DFATs (SC-DFATs). Methods: Mature adipocytes isolated from IFP and SC in osteoarthritis patients (n = 7) were cultured by ceiling culture method to generate DFATs. Obtained IFP-DFATs and SC-DFATs were subjected to flow cytometric and microarray analysis to compare their immunophenotypes and gene expression profiles. Cell proliferation assay and adipogenic, osteogenic, and chondrogenic differentiation assays were performed to evaluate their functional properties. Results: DFATs could be prepared from IFP and SC with similar efficiency. IFP-DFATs and SC-DFATs exhibited similar immunophenotypes (CD73+, CD90+, CD105+, CD31-, CD45-, HLA-DR-) and tri-lineage (adipogenic, osteogenic, and chondrogenic) differentiation potential, consistent with the minimal criteria for defining MSCs. Microarray analysis revealed that the gene expression profiles in IFP-DFATs were very similar to those in SC-DFATs, although there were certain number of genes that showed different levels of expression. The proliferative activity in IFP-DFATs was significantly (p