Fatty Acid–Binding Protein 4 (FABP4) Is Associated with Cartilage Thickness in End-Stage Knee Osteoarthritis

Schadler, Paul; Lohberger, Birgit; Thauerer, Bettina; Faschingbauer, M.; Kullich, W.; Stradner, Martin; Husic, Rusmir; Leithner, Andreas; Steinecker-Frohnwieser, Bibiane

doi:10.1177/19476035211011520

Cited by 7 publications

(13 citation statements)

References 46 publications

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“…Previous studies have reported that downregulation of FABP4 promotes osteoclast formation (9). However, contrary to our findings, it has been reported that FABP4 is up-regulated in SF and plasma in individuals with OA (10, 11). Follistatin-like protein 3 (FSTL3) is a glycoprotein that is involved in regulating inflammation and suppresses osteoblast differentiation of bone marrow mesenchymal cells during that process(12).…”

Section: Discussioncontrasting

confidence: 99%

Altered co-expression patterns of synovial fluid proteins related to the immune system and extracellular matrix organization in late stage OA, compared to non-OA controls

Lonsjo

Rydén

Turkiewicz

et al. 2023

Preprint

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Objective Synovial fluid contains proteins that may have been released from surrounding tissues, our aim was to gain new insights into the proteomic profiles of human synovial fluid in knees with and without osteoarthritis (OA). Methods We used synovial fluid from 11 patients with end-stage medial compartment knee OA, aspirated during total knee replacement, and from 13 deceased donors who had no prior history of knee OA (healthy controls). These samples were analyzed using high-multiplex immunoassays. The differential expression of proteins between the groups was analyzed using a linear mixed effects model. The linear associations between pairs of protein expressions were estimated with a linear regression model. Results We found that almost half of the detected proteins were differentially expressed between the OA and non-OA controls. The proteins that were most elevated in the OA group compared to controls were tartrate-resistant acid phosphatase type 5 (fold change 10.6, 95% CI [6.6-17.0]), coagulation factor XI (4.3 [2.6-6.8]) and urokinase-type plasminogen activator (4.3 [2.3-6.8]). The proteins with lower levels in OA compared to controls were fatty acid-binding protein, adipocyte (0.03 [0.02-0.05]), myocilin (0.05 [0.03-0.08]) and carbonic anhydrase 3 (0.14 [0.09-0.23]). The protein-protein co-expression analysis suggests an overall lower number of protein pairs that show co-expression in OA. Conclusion There is a substantial change in protein abundance in synovial fluid in end-stage knee OA, suggesting that global joint homeostasis is severely deranged. Our findings suggest altered co-expression between the immune response and extracellular matrix organization in end-stage knee OA, in comparison to non-OA controls.

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Section: Discussioncontrasting

confidence: 99%

Altered co-expression patterns of synovial fluid proteins related to the immune system and extracellular matrix organization in late stage OA, compared to non-OA controls

Lonsjo

Rydén

Turkiewicz

et al. 2023

Preprint

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“…Our pilot data also demonstrated that FABP4 has effects on chondrocytes in a dose‐dependent manner 3 . Similar results were observed in other studies investigating the role of FABP4 in OA 13,14 . The role of FABP4 in rheumatoid arthritis has also been recently reported 28 .…”

Section: Discussionsupporting

confidence: 90%

Fatty acid binding protein 4 (FABP4) induces chondrocyte degeneration via activation of the NF‐κb signaling pathway

Zhang,

Lin,

et al. 2023

The FASEB Journal

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The pathogenesis of osteoarthritis (OA) is still unclear. Fatty acid binding protein 4 (FABP4), a novel adipokine, has been found to play a role in OA. This study aimed to explore the role of NF‐κB in FABP4‐induced OA. In the in vivo study, four pairs of 12‐week‐old male FABP4 knockout (KO) and wild‐type (WT) mice were included. The activation of NF‐κB was assessed. In parallel, 24 6‐week‐old male C57/Bl6 mice were fed a high‐fat diet (HFD) and randomly allocated to four groups: daily oral gavage with (1) PBS solution; (2) QNZ (NF‐κB‐specific inhibitor, 1 mg/kg/d); (3) BMS309403 (FABP4‐specific inhibitor, 30 mg/kg/d); and (4) BMS309403 (30 mg/kg/d) + QNZ (1 mg/kg/d). The diet and treatment were sustained for 4 months. The knee joints were obtained to assess cartilage degradation, NF‐κB activation, and subchondral bone sclerosis. In the in vitro study, a mouse chondrogenic cell line (ATDC5) was cultured. FABP4 was supplemented to stimulate chondrocytes, and the activation of NF‐κB was investigated. In parallel, QNZ and NF‐κB‐specific siRNA were used to inhibit NF‐κB. In vivo, the FABP4 WT mice had more significant NF‐κB activation than the KO mice. Dual inhibition of FABP4 and NF‐κB alleviated knee OA in mice. FABP4 has no significant effect on the activation of the JNK signaling pathway. In vitro, FABP4 directly activated NF‐κB in chondrocytes. The use of QNZ and NF‐κB‐siRNA significantly alleviated the expression of catabolic markers of chondrocytes induced by FABP4. FABP4 induces chondrocyte degeneration by activating the NF‐κB pathway.

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“…FABP4 is expressed in vascular endothelial cells of meningiomas, especially anaplastic meningiomas, and may serve as a potential marker (Lee et al, 2021b). A small sample size study found a negative correlation between FABP4 and cartilage thickness in end-stage knee osteoarthritis (Schadler et al, 2021). Other studies have shown that FABP4 is associated with kidney stone formation, and downregulation of FABP4 drives calcification, suggesting a link between kidney stones and metabolic syndrome (Taguchi et al, 2020).…”

Section: Othersmentioning

confidence: 98%

FABP4 in obesity-associated carcinogenesis: Novel insights into mechanisms and therapeutic implications

Liu

Fan

et al. 2022

Front. Mol. Biosci.

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The increasing prevalence of obesity worldwide is associated with an increased risk of various diseases, including multiple metabolic diseases, cardiovascular diseases, and malignant tumors. Fatty acid binding proteins (FABPs) are members of the adipokine family of multifunctional proteins that are related to fatty acid metabolism and are divided into 12 types according to their tissue origin. FABP4 is mainly secreted by adipocytes and macrophages. Under obesity, the synthesis of FABP4 increases, and the FABP4 content is higher not only in tissues but also in the blood, which promotes the occurrence and development of various cancers. Here, we comprehensively investigated obesity epidemiology and the biological mechanisms associated with the functions of FABP4 that may explain this effect. In this review, we explore the molecular mechanisms by which FABP4 promotes carcinoma development and the interaction between fat and cancer cells in obese circumstances here. This review leads us to understand how FABP4 signaling is involved in obesity-associated tumors, which could increase the potential for advancing novel therapeutic strategies and molecular targets for the systematic treatment of malignant tumors.

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Fatty Acid–Binding Protein 4 (FABP4) Is Associated with Cartilage Thickness in End-Stage Knee Osteoarthritis

Cited by 7 publications

References 46 publications

Altered co-expression patterns of synovial fluid proteins related to the immune system and extracellular matrix organization in late stage OA, compared to non-OA controls

Altered co-expression patterns of synovial fluid proteins related to the immune system and extracellular matrix organization in late stage OA, compared to non-OA controls

Fatty acid binding protein 4 (FABP4) induces chondrocyte degeneration via activation of the NF‐κb signaling pathway

FABP4 in obesity-associated carcinogenesis: Novel insights into mechanisms and therapeutic implications

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