Abstract
Objective: Trefoil factor family peptide 3 (TFF3) has been shown to support catabolic functions in cases of osteoarthritis (OA). As in joint physiology and diseases such as OA, the synovial membrane (SM) of the joint capsule also plays a central role. We analyze the ability of SM to produce TFF compare healthy SM and its secretion product synovial fluid (SF) with SM and SF from patients suffering from OA or rheumatoid arthritis (RA). Methods: Real-time PCR and ELISA were used to measure the expression of TFFs in healthy SM and SM from patients suffering from OA or RA. For tissue localization, we investigated TFF1-3 in differently aged human SM of healthy donors by means of immunohistochemistry, real-time PCR and Western blot. Results: Only TFF3 but not TFF1 and -2 was expressed in SM from healthy donors as well as cases of OA or RA on protein and mRNA level. In contrast, all three TFFs were detected in all samples of SF on the protein level. No significant changes were observed for TFF1 at all. TFF2 was significantly upregulated in RA samples in comparison to OA samples. TFF3 protein was significantly downregulated in OA samples in comparison to healthy samples and cases of RA significantly upregulated compared to OA. In contrast, in SM TFF3 protein was not significantly regulated. Conclusion: The data demonstrate the production of TFF3 in SM. Unexpectedly, SF contains all three known TFF peptides. As neither articular cartilage nor SM produce TFF1 and TFF2, we speculate that these originate with high probability from blood serum.
Highlights
In vertebrates, joints have evolved into highly conserved organs that are essential for locomotion
We found that trefoil factor (TFF) peptides are absent in healthy articular cartilage, but in certain disease states, such as osteoarthritis (OA) or septic arthritis, the TFF family member Trefoil factor family peptide 3 (TFF3) supports catabolic functions and links inflammation to tissue remodeling processes, which distinguishes TFF3 as a potential factor in the pathogenesis of OA [19]
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Summary
Joints have evolved into highly conserved organs that are essential for locomotion. Their joint capsules are lined with a synovial membrane (SM), which secretes synovial fluid (SF) and is essential for maintaining the functionality of the joint connections. SM is the innermost membrane of the joint capsule in diarthroses, consisting of an intimal layer comprising 1–2 cells and a subintimal layer containing blood vessels, adipocytes, fibroblasts, and macrophages [1]. Several studies have described TFFs primarily as secretory peptides of the gastrointestinal tract [10]. These were later found in various other tissues all over the body [11]
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