The cellular microenvironment: a new target in the search for cellular and molecular treatment for Dupuytren’s disease

Abstract

Introduction: Dupuytren’s disease (DD) is a debilitating fibrotic disease of the palmar fascia (PF) that leads to irreversible flexion contractures of the fingers and loss of dexterity and hand function. Currently, DD is treated by surgical or enzymatic elimination of the contracted PF using treatment approaches that carry significant morbidity and high recurrence rates.Areas covered: This review is limited to the most recent data pertaining to the cellular and molecular biology of DD. It does not review data on the clinical management of DD.Expert opinion: The current gold standard of treatment of DD is (sub)-total resection of the diseased, contracted palmar fascia. Like other less invasive treatment alternatives, such as needle aponeurotomy or clostridial collagenase digestion of the contracted cords, fasciectomy is associated with high disease recurrence rates. This review summarizes the published evidence that changes in the cellular microenvironment can modify established signaling pathways and gene expression profiles in DD cells. These findings have implications for research programs that aim to identify disease-associated cytokines or growth factors as targets for molecular therapy. A theoretical framework is described, suggesting that future research into new non-surgical treatment approaches for DD should include consideration of the modifying influences of the DD microenvironment. The ultimate aim of DD research should be the development of a treatment that establishes normal cellular homeostasis in the PF and not simply the elimination of PF contractures.