Transforming Growth Factor-Beta (TGF-Β) Regulates Nerve Growth Factor and Cyclooxygenase-2 Expression in Subsynovial Connective Tissue in Patients with Carpal Tunnel Syndrome

Background: It has been reported that transforming growth factor-beta (TGF-β) is elevated in the subsynovial connec tive tissues (SSCTs) of patients with idiopathic carpal tunnel syndrome (CTS) and TGF-β induced fibrosis of SSCTs. A TGF-β-mediated pathway may be a potential target for CTS therapy. Cycloxygenase-2 (COX-2) and nerve growth factor (NGF) are regulated by TGF-β and are associated with fi brosis in several tissues; however, regulation in SSCTs has not been fully clarified. Methods: Forty-three SSCTs were sampled from 35 pa tients undergoing carpal tunnel release (CTR) surgery. Cor relation between TGF-β mRNA and protein expression and COX-2 and NGF were evaluated using quantitative PCR (q-PCR) analysis of total RNA sampled from the SSCTs. To investigate regulation of COX-2 and NGF by TGF-β, cul tured SSCT cells were stimulated with TGF-β and COX-2 and NGE mRNA and protein expression were evaluated us ing q-PCR and western blotting. Results: TGF-β-, NGF-, and COX-2-positive cells were ob served in SSCTs. Expression of COX-2 and NGF positively correlated with TGF-β mRNA expression in the SSCTs of CTS patients (COX-2, r = 0.629, p < 0.001; NGF, r = 0.521, p < 0.001). The expression of COX-2 and NGF mRNA and protein increased significantly in SSCT cells following ex ogenous treatment with TGF-β compared to vehicle-treated cells (p < 0.05). Conclusions: TGF-β may regulate COX-2 and NGF in the SSCTs of CTS patients.