{"doi":"10.1016/j.jhsg.2023.06.017","title":"Let’s Focus on the Fibrosis in Dupuytren Disease: Cell Communication Network Factor 2 as a Novel Target","abstract":"Dupuytren disease is a progressive, benign fibroproliferative disorder of the hands that can lead to debilitating hand contractures. Once symptomatic, treatment involves either surgical intervention, specifically fasciectomy or percutaneous needle aponeurotomy, or enzymatic degradation with clostridial collagenase. Currently, collagenase is the only pharmacotherapy that has been approved for the treatment of Dupuytren contracture. There is a need for a pharmacotherapeutic that can be administered to limit disease progression and prevent recurrence after treatment. Targeting the underlying fibrotic pathophysiology is critical. We propose a novel target to be considered in Dupuytren disease—cell communication network factor 2/connective tissue growth factor—an established mediator of musculoskeletal tissue fibrosis. Dupuytren disease is a progressive, benign fibroproliferative disorder of the hands that can lead to debilitating hand contractures. Once symptomatic, treatment involves either surgical intervention, specifically fasciectomy or percutaneous needle aponeurotomy, or enzymatic degradation with clostridial collagenase. Currently, collagenase is the only pharmacotherapy that has been approved for the treatment of Dupuytren contracture. There is a need for a pharmacotherapeutic that can be administered to limit disease progression and prevent recurrence after treatment. Targeting the underlying fibrotic pathophysiology is critical. We propose a novel target to be considered in Dupuytren disease—cell communication network factor 2/connective tissue growth factor—an established mediator of musculoskeletal tissue fibrosis. Research into fibroproliferative disorders continues to expand our knowledge of the underlying mechanisms behind disorders such as idiopathic pulmonary fibrosis, Dupuytren disease (DD), scleroderma, and Peyronie disease. As a result, potential therapeutics for targeting these diseases are being identified. Although newer pharmacotherapies are being developed, there has also been interest in repurposing medications already approved by the US Food and Drug Administration for the treatment of fibrotic disorders.1Karatzas E. Kakouri A.C. Kolios G. Delis A. Spyrou G.M. Fibrotic expression profile analysis reveals repurposed drugs with potential anti-fibrotic mode of action.PLOS ONE. 2021; 16e0249687Crossref PubMed Scopus (5) Google Scholar, 2Rosenbloom J. Mendoza F.A. Jimenez S.A. Strategies for anti-fibrotic therapies.Biochim Biophys Acta. 2013; 1832: 1088-1103Crossref PubMed Scopus (147) Google Scholar, 3Tai Y. Woods E.L. Dally J. et al.Myofibroblasts: function, formation, and scope of molecular therapies for skin fibrosis.Biomolecules. 2021; 11: 1095Crossref PubMed Scopus (67) Google Scholar Despite these efforts, the mainstay of treatment for symptomatic Dupuytren contracture is largely surgical. The most common nonsurgical treatment is local collagenase injection for enzymatic degradation. To date, collagenase treatment is the only Food and Drug Administration–approved pharmacotherapy in DD. There is a need for additional pharmacotherapeutic options that target the underlying fibrotic response, thereby halting early disease progression, reversing fibrosis once the disease has progressed, and, in doing so, potentially avoiding the risks of invasive treatments. The fibroproliferation underlying DD affects the palmar fascia of the hand and digits. The clinical course can lead to symptomatic contractures, ultimately resulting in functionally limiting declines in range of motion and diminished quality of life.4Shih B. Bayat A. Scientific understanding and clinical management of Dupuytren disease.Nat Rev Rheumatol. 2010; 6: 715-726Crossref PubMed Scopus (124) Google Scholar The natural history of DD was initially described, by Luck5Luck J.V. Dupuytren’s contracture; a new concept of the pathogenesis correlated with surgical management.J Bone Joint Surg Am. 1959; 41-A: 635-664Crossref PubMed Scopus (244) Google Sc","journal":"Journal of Hand Surgery Global Online","year":2023,"id":367231,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":5,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9563,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1124387,"name":"Nathan T. Morrell","orcid":"0000-0001-6800-1753","position":1,"is_corresponding":false},{"id":386280,"name":"Steven N. Popoff","orcid":null,"position":2,"is_corresponding":false},{"id":1052083,"name":"Prosper Benhaim","orcid":"0000-0001-8861-811X","position":3,"is_corresponding":false},{"id":342175,"name":"Mary F. Barbe","orcid":"0000-0002-5235-9803","position":4,"is_corresponding":false},{"id":1052082,"name":"Alex G. Lambi","orcid":"0000-0003-4711-1931","position":0,"is_corresponding":true}],"reference_count":66,"raw_metadata":null,"created_at":"2026-07-19T01:15:12.215513Z","pmid":"37790821","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}