Infrapatellar Fat Pad Changes Research Articles

Inhibitory effect of low‑intensity pulsed ultrasound on the fibrosis of the infrapatellar fat pad through the regulation of HIF‑1α in a carrageenan‑induced knee osteoarthritis rat model.

Fibrotic changes in the infrapatellar fat pad (IFP) are involved in the pathogenesis of knee osteoarthritis (KOA). HIF-1α is a transcription factor that is activated during hypoxia and is suggested to play a role in fibrosis in various organs. However, its participation in the fibrotic changes in IFP remains unclear. Therefore, we investigated the role of HIF-1α in IFP fibrosis using a carrageenan-induced KOA rat model and evaluated the potential of low-intensity pulsed ultrasound (LIPUS) as a novel treatment for KOA. A rat model was prepared by intra-articular injection of 0.5% carrageenan (50 µl) using 8-week-old male Wistar rats. Fibrosis of the IFP was evaluated histologically by hematoxylin and eosin and Sirius Red staining at 1 and 2 weeks after intra-articular injection. The mRNA expression levels of HIF-1α and fibrosis-related molecules, CTGF and VEGF, were analyzed using reverse transcription-quantitative PCR, and the DNA binding activity of HIF-1α was assessed using a binding assay. In addition, the effect of irradiation with LIPUS on the fibrosis of IFP was verified. Histological studies demonstrated a significant increase in the fibrosis of IFP 1 and 2 weeks after intra-articular injection of carrageenan, accompanied by overexpression of CTGF and VEGF, which was followed by upregulation of transcriptional activation of HIF-1α. Moreover, intervention with LIPUS for 2 weeks after injection of carrageenan attenuated fibrosis of IFP, accompanied by a significant reduction in the transcriptional activation of HIF-1α and decreased the gene expression levels of HIF-1α, CTGF, and VEGF. The present study demonstrated that activation of HIF-1α promoted fibrosis of IFP in carrageenan-induced arthritis in rats and that intervention with LIPUS decreased the activity of HIF-1α and inhibited fibrosis. These results suggest that LIPUS may serve as a novel approach for the treatment of KOA, through its modulation of HIF-1α.

RELATIONSHIP BETWEEN INFRAPATELLAR FAT PAD CHANGES AND ANTERIOR KNEE PAIN IN PATIENTS WITH KNEE OSTEOARTHRITIS

Purpose: Infrapatellar fat pad (IPFP) plays several biomechanical roles such as stabilizing patella, improving efficiency of extensor mechanism. Recently, IPFP has been received attention in pathophysiology of knee osteoarthritis (OA). However, it is unknown how IPFP changes as knee OA progresses. In addition, IPFP is nerve-rich tissue. Although previous reports indicate that IPFP is the source of pain, the characteristics of IPFP in patients with knee OA with anterior knee pain are often unclear.

Inhibition of fibrotic changes in infrapatellar fat pad alleviates persistent pain and articular cartilage degeneration in monoiodoacetic acid-induced rat arthritis model

We have reported that fibrotic changes in infrapatellar fat pad (IFP) after acute joint inflammation are closely associated with persistent pain in rats. In this study, to examine the effects of anti-fibrotic treatment on persistent pain, we used C-type natriuretic peptides (CNP) at the recovery phase after acute joint inflammation. Thirty-two male Wistar rats were used in this study. Monoiodoacetic acid (MIA) was injected intra-articularly to induce IFP fibrosis and persistent pain. CNP was injected after acute inflammatory phase in the same knee joint. Time-course pain-avoidance behavior tests and histological analyses were performed to examine the effects of CNP. Histological evaluations indicated that intra-articular injection of CNP inhibited fibrotic changes in IFP after acute inflammation. Incapacitance tests indicated that MIA injection into rat knee joint quickly decreased the percent weight on ipsilateral limb. In the vehicle group, the decrease was maintained up to day 28, suggesting that pain persistence occurred after acute inflammation (Day 0/Day 28, Est Dif-8.15, CI -10.78∼-5.53, Linear mixed-effect model). In contrast, the pain was alleviated in the CNP group after day 14 (Day0/Day 14, -0.51,-2.62-1.59). In addition, we observed significant improvement in the degree of articular cartilage degeneration at day 14 in the CNP group (OARSI score: vehicle 16.14±4.37 vs CNP 6.87±3.44, P<0.01; Wilcoxon rank sum test). Fibrotic changes in IFP may play important roles in both persistent pain and articular cartilage degeneration.

High-fat feeding primes the mouse knee joint to develop osteoarthritis and pathologic infrapatellar fat pad changes after surgically induced injury

Obesity is one of the greatest risk factors for osteoarthritis (OA) and evidence is accumulating that inflammatory mediators and innate immunity play an important role. The infrapatellar fat pad (IPFP) could be a potential local source of inflammatory mediators in the knee. Here, we combine surgical joint damage with high-fat feeding in mice to investigate inflammatory responses in the IPFP during OA development. Mice (n=30) received either a low-fat diet (LFD), high-fat diet (HFD) for 18 weeks or switched diets (LFD>HFD) after 10 weeks. OA was induced by surgical destabilization of the medial meniscus (DMM), contralateral knees served as sham controls. An additional HFD-only group (n=15) received no DMM. The most pronounced inflammation, characterized by macrophage crown-like structures (CLS), was found in HFD+DMM mice, CLS increased compared to HFD only (mean difference=7.26, 95%CI [1.52-13.0]) and LFD+DMM (mean difference=6.35, 95%CI [0.53-12.18). The M1 macrophage marker iNOS increased by DMM (ratio=2.48, 95%CI [1.37-4.50]), while no change in M2 macrophage marker CD206 was observed. Fibrosis was minimal by HFD alone, but in combination with DMM it increased with 23.45% (95%CI [13.67-33.24]). These findings indicate that a high-fat dietalone does not trigger inflammation or fibrosis in the infrapatellar fat pad, but in combination with an extra damage trigger, like DMM, induces inflammation and fibrosis in the infrapatellar fat pad. These data suggest that HFD provides a priming effect on the infrapatellar fat pad and that combined actions bring the joint in a metabolic state of progressive OA.

Daily and short-term application of joint movement for the prevention of infrapatellar fat pad atrophy due to immobilization.

[Purpose] To mobilize the knee joint during cast fixation and to determine whether infrapatellar fat pad changes can be prevented. [Materials and Methods] We randomly allocated Wistar rats into 3 groups as follows: normal group, raised in normal conditions (n=5); contracture group, immobilized with cast fixation (n=5); and prevention group, treated with joint movement during immobilization (n=5). We immobilized the right hindlimb using cast fixation. Joint movement in the prevention group was accomplished by repeatedly pulling the right hindlimb caudally and then returning the leg to the bent position for 10 minutes every day for 2 weeks. We used a metronome to maintain a constant speed, with one set lasting 2 seconds (1-second traction and 1-second return). [Results] The contracture group had adipose cells of various sizes and fibrosis in the infrapatellar fat pad. These changes were also found in milder forms in the prevention group. We found significant differences in the cross section of adipose cells and in knee extension restriction between the groups. [Conclusion] Promoting joint movement may not only have a therapeutic effect on adipose cells but also a preventative effect.

Histopathological changes in the infrapatellar fat pad in an experimental rabbit model of early patellofemoral osteoarthritis

BackgroundThe purpose of this study was to characterise the histopathological changes in the infrapatellar fat pad (IPFP) in the early stage of patellofemoral osteoarthritis (PFOA). MethodsSixty-four New Zealand white rabbits were randomly divided into experimental (n = 24), sham (n = 16), and control groups (n = 24). In the experimental group, denoted as the patellar ligament uneven shortening group (US group), the patellar ligament (PL) was folded eight millimetres and sutured. After eight weeks, all animals were euthanised, and magnetic resonance imaging (MRI) evaluation, wet IPFP weight measurement, and histopathological and immunohistochemistry analysis were performed to analyse the histopathological changes in the IPFPs. ResultsThe maximum cross-sectional area (CSA) of the IPFPs in the sagittal position of MRI in the control group, sham group, and US group were 45.50 ± 7.19 mm2, 45.88 ± 6.60 mm2 (vs. control group, P = 0.907), and 53.83 ± 8.24 mm2 (vs. control group, P = 0.015; vs. sham group, P = 0.035), respectively. The MRI intensity of the IPFPs in the control group, sham group, and US group were 115.53 ± 28.85, 108.53 ± 26.73 (vs. control group, P = 0.589), and 154.52 ± 18.48 (vs. control group, P = 0.002; vs. sham group, P = 0.002), respectively. The wet weight of the IPFPs in the control group, sham group, and US group were 0.32 ± 0.05 g, 0.32 ± 0.04 g (vs. control group, P = 0.895), and 0.38 ± 0.06 g (vs. control group, P = 0.017; vs. sham group, P = 0.033), respectively. The Osteoarthritis Research Society International (OARSI) scores of the IPFPs in the US group were 6.00 ± 1.91, which was higher than the scores of 2.50 ± 2.02 (P < 0.001) in the control group and of 2.75 ± 1.67 (P = 0.001) in the sham group. ConclusionsThe histopathological changes of the IPFPs as determined via MRI and microscopic structure appeared to occur much earlier than cartilage damage in PFOA. Furthermore, detecting and treating the IPFP changes may offer aid in the diagnosis and treatment of PFOA.

Pain induced by injection of hypertonic saline into the infrapatellar fat pad and effect on coordination of the quadriceps muscles

Musculoskeletal conditions of the knee involve changes in sensorimotor function, but it is unclear whether these changes are a cause or result of pain. Induction of experimental pain may help solve this issue. Although this is commonly achieved by injection of hypertonic saline into muscle, muscle is commonly not the source of pain. This study investigated whether pain induced by injection of saline into the infrapatellar fat pad changes motor control of the quadriceps muscles of the knee. Ten participants performed a standardized task involving ascending and descending a series of steps. Electromyographic activity (EMG) of vastus medialis obliquus (VMO) and vastus lateralis (VL) was recorded with surface electrodes. Trials were conducted without pain, with anterior knee pain induced by injection (0.25 ml) of hypertonic saline (5%) into the infrapatellar fat pad, with anticipation of pain associated with unpredictable electrical shocks to the knee, and 20 minutes after pain cessation. EMG onset and amplitude were analyzed. When participants ascended the steps with pain, the onset of VMO EMG was delayed relative to that of VL, in contrast to simultaneous or earlier activation of VMO EMG in the pre- and postpain trials. VL EMG amplitude was decreased significantly from the control condition. These data show that alterations in coordination of knee muscle activity can be caused by pain, even when it is of nonmuscle origin. Treatment of pain is therefore important to facilitate performance of the quadriceps muscles, which are essential for locomotor and functional tasks as well as for knee stability.