Shared Extracellular Matrix Remodeling and Proteomic Signature in Dupuytren's Disease and Relapsed Clubfoot Tissue

Although Dupuytren's disease (DD) and relapsed Clubfoot (RC) are clinically distinct conditions, both exhibit fibrotic tissue remodeling and contracture. This exploratory study investigated whether DD and RC share molecular features associated with fibroproliferative contracture. Pathological tissues from DD nodules and contracted tissues from RC together with their respective control tissues (n = 6/group), were analyzed using label-free quantitative proteomics. The analysis identified 12 significantly upregulated proteins shared between both pathological conditions relative to their controls (|log₂FC| ≥ 1, p ≤ 0.05). These proteins included structural, signaling and tensile stress ECM proteins. Functional enrichment and network analyses revealed partially overlapping dysregulation of pathways associated with ECM organization and degradation, ECM-receptor interaction, matricellular signaling and mechanobiological processes. In DD samples (n = 10), immunohistochemistry confirmed increased expression of fibrosis-associated proteins (α-SMA, TGF-β1, TGFBI, COL III, COL VI, and COL XII) (at least p < 0.01). Despite these similarities, differences in individual protein abundance and collagen crosslinking were observed between tissues. The findings suggest that DD and RC may share aspects of fibrotic ECM-remodeling despite differences in age, localization, and disease origin. These findings provide initial insights into shared ECM-remodeling processes, although their interpretation should consider the relatively small sample size and biological heterogeneity of the analyzed tissues.