Dupuytren’s disease is one of the most common fibroses of the hand. Firm nodules and cords form in the palm, gradually pulling the fingers towards the palm and making it impossible to straighten them. A similar fate awaits some children born with a congenital foot deformity known as clubfoot, in whom the deformity often recurs after treatment. The causes of these conditions remain poorly understood, and no effective drug capable of preventing the fibrotic remodelling of the tissue currently exists. Two new studies by scientists from the Institute of Physiology CAS (IPHYS) and their clinical partners provide a detailed molecular description of the diseased tissue in both disorders, along with the first three-dimensional laboratory model of Dupuytren’s disease, which can be used to test antifibrotic compounds.
Hand and Foot Speak a Similar Molecular Language
Fibrosis is the excessive accumulation of connective tissue, especially collagen, which gives tissue its shape and strength. In the new study, the researchers compared diseased tissue from two diagnoses that appear very different at first sight: palmar nodules in Dupuytren’s disease, which mainly affects men over the age of fifty, and fibrotic tissue in a congenital disorder in children that repeatedly causes deformity of the foot. “Using advanced analytical methods, we identified thousands of proteins in the healthy samples as well as in both types of diseased tissue. By comparing them, we uncovered the molecular details of the remodelling and degradation of the extracellular matrix and found that these diseases share a similar basis – above all, the excessive production of extracellular matrix proteins and increased blood supply to the affected tissue,” explains Adam Eckhardt from the Laboratory of Translational Metabolism at IPHYS.
A Three-Dimensional Disease Model as a Testing Platform
Another aim of the research is to find a compound that would slow the disease down at an early stage, that is, before the affected tissue has to be surgically removed. The newly developed complex three-dimensional laboratory model of Dupuytren’s disease could serve this purpose. “This is an entirely new three-dimensional model of living tissue, whose functionality we have already verified. Adding minoxidil, a substance known from hair-loss products that also blocks the enzymes responsible for collagen cross-linking, led to a marked reduction in the production of soluble collagen as well as in the levels of proteins associated with fibrosis and inflammation,” says Jarmila Knitlová, first author of the study, from the Laboratory of Biomaterials and Tissue Engineering at IPHYS. In two-dimensional culture (for example, on a commonly used plastic dish), the same compound produced no statistically significant change. The new model can therefore reveal effects that conventional cell cultures miss entirely.
Significance for Patients
Together, the two studies form an interconnected whole. The first shows which proteins and signalling pathways are altered in the same way across fibrotic disorders of the musculoskeletal system, providing a list of candidate treatment targets and biomarkers for disease monitoring. The second provides a tool on which such targets and compounds can be tested. This opens the way to the search for new compounds for the treatment of fibrotic diseases.
Reference:
Knitlova J., Eckhardt A., Hadraba D., Vondrasek D., Stachon R., Filova E., Jencova V., Havlickova K., Kobets T., Ostadal M., and Bacakova L.: Development of a 3D In Vitro Model of Dupuytren’s Disease as a Platform for Drug Screening. Cell Mol Bioeng 19, 111-127 (2026). IF = 3.5; DOI: 10.1007/s12195-026-00885-2
Novotny T., Eckhardt A., Knitlova J., Doubkova M., Stachon R., Hrdina F., Kobets T., and Ostadal M.: Shared Extracellular Matrix Remodeling and Proteomic Signature in Dupuytren’s Disease and Relapsed Clubfoot Tissue. Cells 15(2026). IF = 6.0; DOI: 10.3390/cells15110977
The studies were carried out in collaboration between the IPHYS and the Department of Orthopaedics of Bulovka University Hospital and the First Faculty of Medicine of Charles University, Masaryk Hospital in Ústí nad Labem and Jan Evangelista Purkyně University, the Second Faculty of Medicine of Charles University in Prague, the Faculty of Science of Charles University, the Institute of Molecular Genetics of the Czech Academy of Sciences, and the Technical University of Liberec.
