Infrapatellar fat pad features in osteoarthritis: a histopathological and molecular study

Favero, Marta; El-Hadi, Hamza; Belluzzi, Elisa; Granzotto, Marnie; Porzionato, Andrea; Sarasin, Gloria; Rambaldo, Anna; Iacobellis, Claudio; Cigolotti, Augusto; Fontanella, Chiara Giulia; Natali, Arturo N.; Ramonda, Roberta; Ruggieri, Pietro; De, Raffaele; Vettor, Roberto; Rossato, Marco; Macchi, Veronica

doi:10.1093/rheumatology/kex287

Cited by 139 publications

(185 citation statements)

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“…In accordance to this, studies could show a proinflammatory cytokine profile in the IPFP, by detection of, for example, TNF‐α, VEGF (vascular endothelial growth factor) and IL‐6 . Favero et al found a different cytokine profile in the fat pad of osteoarthritic patients compared with a control group of an organic‐donor program. However, it has to be mentioned, that the donors of the control group had a mean age of 81 years, which makes the exclusion of osteoarthritic changes, even if there were no clinical symptoms known, quite difficult.…”

mentioning

confidence: 72%

“…Moreover, it seems, that the IPFP could be involved in the inflammatory reaction pathognomonic for OA, as in an animal model, the injection of arthritogenic factor led to synovitis of Hoffa's synovia, infiltration with neutrophils and mononuclear cells and fat necrosis . Recent studies have shown that also the IPFP secretes proinflammatory cytokines and may modulate the inflammatory processes contributing to the pathomechanism of knee OA . A higher gene expression of IL‐6 was found in mesenchymal stem cells from the fad pad of OA patients compared with a control group of patients with an ACL rupture .…”

Section: Discussionmentioning

confidence: 98%

“…With magnet resonance imaging (MRI), no difference in the volume could be detected, compared with a control group, but inflammatory changes could be found . In accordance to this, studies could show a proinflammatory cytokine profile in the IPFP, by detection of, for example, TNF‐α, VEGF (vascular endothelial growth factor) and IL‐6 . Favero et al found a different cytokine profile in the fat pad of osteoarthritic patients compared with a control group of an organic‐donor program.…”

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confidence: 86%

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COMP in the Infrapatellar Fat Pad—Results of a Prospective Histological, Immunohistological, and Biochemical Case–Control Study

Grevenstein

Heilig

Dargel

et al. 2019

Journal Orthopaedic Research

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Knee osteoarthritis (OA) involves several structures and molecules in the joint, which interact in a pathophysiological process. One of these molecules is the cartilage oligomeric matrix protein (COMP). Elevated COMP levels in the synovial fluid as well as in the serum have been described in OA patients. However, this has not been described in the infrapatellar fat pad (IPFP) tissue before. In this prospective trial, we collected 14 IPFPs from patients with high‐grade OA (mean age 63.8 ± 17.6 years) who underwent total knee replacement (OA group) and from 11 healthy patients (mean age 33.7 ± 14.8 years) who underwent anterior cruciate ligament reconstruction (control group). The presence of macrophages (CD68 and CD206) and proinflammatory cytokines (interleukin 1β [IL‐1β] and IL‐6) was analyzed. Histological and immunohistological examinations as well as immunoblotting analysis for COMP, leptin, and matrix‐metalloproteinase‐3 were performed. The IPFPs of both the OA and control group consisted of adipose tissue and fibrous tissue, and the fibrous tissue showed higher score values than the adipose tissue for COMP staining (intensity as well as stained area) in both groups. Although COMP could be detected in most samples, leptin expression was found only in single specimens. COMP could be detected mostly in the fibrous tissue portion of the IPFP. We speculate that it is involved in a remodeling process taking place in the IPFP during OA. Presence of leptin was irregular in immunohistology, and the control group showed higher scores in case of presence. Interestingly, immunoblotting could detect leptin in all analyzed samples. © 2019 The Authors. Journal of Orthopaedic Research® published by Wiley Periodicals, Inc. on behalf of Orthopaedic Research Society J Orthop Res 38:747‐758, 2020

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confidence: 72%

Section: Discussionmentioning

confidence: 98%

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confidence: 86%

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COMP in the Infrapatellar Fat Pad—Results of a Prospective Histological, Immunohistological, and Biochemical Case–Control Study

Grevenstein

Heilig

Dargel

et al. 2019

Journal Orthopaedic Research

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“…In the IFP of patients with OA undergoing total knee replacement, an increase of inflammatory infiltration, vascularization and thickness of the interlobular septa was found. At the same time the synovial membrane adjacent to IFP presented lymphocytic infiltration, hyperplasia and higher vascularization compared with healthy controls (Favero et al 2017). In fact, in an experimental model of OA, marked loss of adipocytes in IFP was associated with extensive synovial proliferation (SP) and subsynovial fibrosis (Clements et al 2009).…”

Section: Histopathologymentioning

confidence: 90%

“…In fact, considering the intra-articular location of the IFP, the metabolic properties of adipose tissue and the fact that the OA involves all articular tissues, it is likely that the IFP could also be involved in OA of the knee (Clockaerts et al 2010). Peculiar microscopic changes in OA IFP, such as thickening of interlobular septa, an increase in vascularization and the presence of inflammatory infiltrates, have been described (Favero et al 2017;Macchi et al 2017). Importantly, these changes have also been observed in the IFP adjacent synovial membrane, suggesting a possible cross-talk between these two structures (Eymard et al 2014), which may support a possible role of IFP in disease progression (Wenham & Conaghan, 2010;Sime et al 2017).…”

Section: Introductionmentioning

confidence: 99%

The infrapatellar fat pad and the synovial membrane: an anatomo‐functional unit

et al. 2018

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

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Blockage of Osteopontin‐Integrin β3 Signaling in Infrapatellar Fat Pad Attenuates Osteoarthritis in Mice

Dai

Zhu

et al. 2023

Advanced Science

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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.

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Infrapatellar fat pad features in osteoarthritis: a histopathological and molecular study

Abstract: OA IFPs and synovial membranes are more inflamed, vascularized and fibrous compared with those of control patients (without OA).

Cited by 139 publications

References 35 publications

COMP in the Infrapatellar Fat Pad—Results of a Prospective Histological, Immunohistological, and Biochemical Case–Control Study

COMP in the Infrapatellar Fat Pad—Results of a Prospective Histological, Immunohistological, and Biochemical Case–Control Study

The infrapatellar fat pad and the synovial membrane: an anatomo‐functional unit

Blockage of Osteopontin‐Integrin β3 Signaling in Infrapatellar Fat Pad Attenuates Osteoarthritis in Mice

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