Human Synovia Contains Trefoil Factor Family (TFF) Peptides 1-3 Although Synovial Membrane Only Produces TFF3: Implications in Osteoarthritis and Rheumatoid Arthritis

Int J Mol Sci. 2019 Dec 3;20(23):6105. doi: 10.3390/ijms20236105.


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.

Keywords: osteoarthritis (OA); rheumatoid arthritis (RA); synovial fluid (SF); synovial membrane (SM); trefoil factor family peptides (TFF).

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Arthritis, Rheumatoid / metabolism*
  • Female
  • Humans
  • Male
  • Middle Aged
  • Osteoarthritis / metabolism*
  • Peptides / metabolism
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Synovial Fluid / metabolism*
  • Synovial Membrane / metabolism*
  • Tissue Donors
  • Trefoil Factor-1 / genetics
  • Trefoil Factor-1 / metabolism*
  • Trefoil Factor-2 / genetics
  • Trefoil Factor-2 / metabolism*
  • Trefoil Factor-3 / genetics
  • Trefoil Factor-3 / metabolism*


  • Peptides
  • RNA, Messenger
  • Trefoil Factor-1
  • Trefoil Factor-2
  • Trefoil Factor-3