The roles of Tenascin C and Fibronectin 1 in adhesive capsulitis: a pilot gene expression study

Abstract

OBJECTIVES:We evaluated mRNA expression levels of genes that encode TGF-β1; the TGF-β1 receptor; the collagen-modifying enzymes LOX, PLOD1, and PLOD2; and the extracellular matrix proteins COMP, FN1, TNC and TNXB in synovial/capsule specimens from patients with idiopathic adhesive capsulitis. Possible associations between the measured mRNA levels and clinical parameters were also investigated.METHODS:We obtained glenohumeral joint synovium/capsule specimens from 9 patients with idiopathic adhesive capsulitis who had not shown improvement in symptoms after 5 months of physiotherapy. Adhesive capsulitis was confirmed in all patients by magnetic resonance imaging. We also obtained specimens from 8 control patients who had underwent surgery for acute acromioclavicular joint dislocation and who had radiological indication of glenohumeral capsule alteration based on arthroscopic evaluation. mRNA expression in the synovium/capsule specimens was analyzed by quantitative reverse transcription PCR. The B2M and HPRT1 genes were used as references to normalize target gene expression in the shoulder tissue samples.RESULTS:The synovium/capsule samples from the patients with adhesive capsulitis had significantly higher TNC and FN1 expression than those from the controls. Additionally, symptom duration directly correlated with expression of TGFβ1 receptor I.CONCLUSION:Elevated levels of TNC and FN1 expression may be a marker of capsule injury. Upregulation of TGFβ1 receptor I seems to be dependent on symptom duration; therefore, TGFβ signaling may be involved in adhesive capsulitis. As such, TNC, FN1 and TGFβ1 receptor I may also play roles in adhesive capsulitis by contributing to capsule inflammation and fibrosis.

Genetic variants involved in extracellular matrix homeostasis play a role in the susceptibility to frozen shoulder: A case‐control study

“…Conversely, TGFBR1 rs1590 is located in the 3′‐UTR region, which is involved in the regulation of mRNA stability, and the rare homozygous variant seems to be associated with increased disease risk. These findings reinforce the involvement of TGFβ signaling in FS, as previously demonstrated by gene expression analysis …”

“…FN1 is among the proteins with a fibronectin type II domain that can be degraded by MMP9. However, FN1, which is increased in the capsule of patients with FS, is also able to induce an increase of MMP9 expression . The feedback between these proteins is important for tissue remodeling because, in this context, MMP9 has been suggested to release or activate a number of cytokines and growth factors, including TGFB1 …”

“…However, both FN1 and TNC glycoproteins act in TGFβ modulation . Increased TNC and FN1 mRNA expression is a possible a marker of capsule injury . Upregulation of TGFBR1 seems also to be dependent on symptom duration, and thus TGFβ signaling may be involved in FS .…”

“…21,22 Increased TNC and FN1 mRNA expression is a possible a marker of capsule injury. 23 Upregulation of TGFBR1 seems also to be Carina dependent on symptom duration, and thus TGFb signaling may be involved in FS. 23 Because TNC, FN1, and TGFBR1 may play a role in FS by contributing to capsule inflammation and fibrosis, we hypothesize that genetic variants in these genes, as well as in COL1A1 and COL5A1, TGFB1, TIMP2, and MMPs, may contribute to the susceptibility to this shoulder condition.…”

Sex differences in tendon structure and function

“…Periostin is a matricellular protein that helps to organize the ECM and participate in integrin‐mediated signaling, but high amounts of periostin are associated with excessively fibrotic tissue repair . Tenascin C is a glycoprotein associated fibroblast migration and proliferation, and increased levels of tenascin C have been associated with inflammation and fibrosis during tissue repair . Fibronectin, periostin, and tenascin C proteins were all highly enriched in female tendons compared to male tendons.…”