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Communications Biology Nov 2023Dupuytren's contracture, a superficial dermal fibrosis, causes flexion contracture of the affected finger, impairing hand function. Specific single-nucleotide...
Dupuytren's contracture, a superficial dermal fibrosis, causes flexion contracture of the affected finger, impairing hand function. Specific single-nucleotide polymorphisms within genes in the Wnt signalling pathway are associated with the disease. However, the precise role of Wnt signalling dysregulation in the onset and progression of Dupuytren's contracture remains unclear. Here, using a fibrosis mouse model and clinical samples of human Dupuytren's contractures, we demonstrate that the activation of Wnt/β-catenin signalling in Tppp3-positive cells in the dermis of the paw is associated with the development of fibrosis. Fibrosis development and progression via Wnt/β-catenin signalling are closely related to stromal cell-macrophage interactions, and Wnt/β-catenin signalling activation in Tppp3-positive stromal cells causes M2 macrophage infiltration via chemokine Cxcl14, resulting in the formation of a TGF-β-expressing fibrotic niche. Inhibition of Cxcl14 mitigates fibrosis by decreasing macrophage infiltration. These findings suggest that Cxcl14-mediated stromal cell-macrophage interaction is a promising therapeutic target for Wnt/β-catenin-induced fibrosis.
Topics: Animals; Mice; Humans; Dupuytren Contracture; beta Catenin; Ligands; Wnt Signaling Pathway; Fibrosis
PubMed: 37980373
DOI: 10.1038/s42003-023-05558-8 -
Cancer Treatment Reviews Feb 2024Desmoid tumors (DT) are rare, slow-growing, locally invasive soft tissue tumors that often pose significant therapeutic challenges. Traditional management strategies... (Review)
Review
Desmoid tumors (DT) are rare, slow-growing, locally invasive soft tissue tumors that often pose significant therapeutic challenges. Traditional management strategies including active surveillance, surgery, radiotherapy, and systemic therapy which are associated with varying recurrence rates and high morbidity. Given the challenging nature of DT and the modest outcomes associated with current treatment strategies, there has been a growing interest in the field of γ-secretase inhibitors as a result of its action on the Wnt/β-catenin signaling pathway. In this review article, we will shed the light on the pathogenesis and molecular biology of DT, discuss its symptoms and diagnosis, and provide a comprehensive review of the traditional therapeutic approaches. We will also delve into the mechanisms of action of γ-secretase inhibitors, its efficacy, and the existing preclinical and clinical data available to date on the use of these agents, as well as the potential challenges and future prospects in the treatment landscape of these tumors.
Topics: Humans; Fibromatosis, Aggressive; Amyloid Precursor Protein Secretases
PubMed: 38159438
DOI: 10.1016/j.ctrv.2023.102675 -
The Journal of Hand Surgery Sep 2023Currently, no treatment corrects the contractile nature of Dupuytren myofibroblasts (DMFs) or prevents recurrence following surgery. Antifibrotic and proadipogenic...
PURPOSE
Currently, no treatment corrects the contractile nature of Dupuytren myofibroblasts (DMFs) or prevents recurrence following surgery. Antifibrotic and proadipogenic growth factors are released when adipose-derived stem cells (ASCs) are cultured with platelet-rich plasma (PRP), a platelet concentration from whole blood. Reprograming myofibroblasts into adipocytes via growth factors is proposed as a powerful potential tool to target fibrosis. We aimed to assess whether the combination of ASCs and PRP reprograms DMFs into adipocytes in vitro and alters their contractile nature in vivo.
METHODS
Normal human dermal fibroblasts (NHDFs) and DMFs from Dupuytren patients were isolated and cocultured with ASCs and PRP either alone or together. Adipocytes were detected by Oil Red O and perilipin staining. DMFs and NHDFs were transplanted into the forepaws of rats (Rowett Nude [rnu/rnu]) and treated with saline, PRP+ASCs, or collagenase Clostridium histolyticum (clinical comparison) 2 months later. After 2 weeks, the tissue was harvested and subjected to Masson trichrome staining, and collagen I and III and alpha-smooth muscle actin detection by immunohistochemistry.
RESULTS
Myofibroblasts transform into adipocytes upon coculture with PRP+ASCs. DMFs show increased alpha-smooth muscle actin expression in vivo compared with NHDFs, which is significantly decreased after PRP+ASCs and collagenase Clostridium histolyticum treatments. DMFs induce collagen I and III expressions in rat paws compared with NHDFs, with a type III to I ratio increase. Treatment with PRP+ASC reduced the ratio, but collagenase Clostridium histolyticum did not.
CONCLUSIONS
Treating DMFs with PRP+ASCs provides factors that induce myofibroblast to adipocyte transformation. This treatment reduces the contractile phenotype and fibrosis markers in vivo. Future studies should detail the mechanism of this conversion.
CLINICAL RELEVANCE
The combination of PRP and ASCs to induce the differentiation of DMFs into adipocytes may serve to limit surgery to a percutaneous contracture release and biological injection, rather than a moderate or radical fasciectomy, and reduce the recurrence of Dupuytren contracture.
Topics: Humans; Animals; Rats; Dupuytren Contracture; Myofibroblasts; Microbial Collagenase; Actins; Collagen Type I
PubMed: 37480917
DOI: 10.1016/j.jhsa.2023.06.007 -
The Bone & Joint Journal Jul 2023Desmoid tumours are a rare fibroblastic proliferation of monoclonal origin, arising in deep soft-tissues. Histologically, they are characterized by locally aggressive...
Desmoid tumours are a rare fibroblastic proliferation of monoclonal origin, arising in deep soft-tissues. Histologically, they are characterized by locally aggressive behaviour and an inability to metastasize, and clinically by a heterogeneous and unpredictable course. Desmoid tumours can occur in any anatomical site, but commonly arise in the limbs. Despite their benign nature, they can be extremely disabling and sometimes life-threatening, causing severe pain and functional limitations. Their surgical management is complex and challenging, due to uncertainties surrounding the biological and clinical behaviour, rarity, and limited available literature. Resection has been the first-line approach for patients with a desmoid tumour but, during the last few decades, a shift towards a more conservative approach has occurred, with an initial 'wait and see' policy. Many medical and regional forms of treatment are also available for the management of this condition, and others have recently emerged with promising results. However, many areas of controversy remain, and further studies and global collaboration are needed to obtain prospective and randomized data, in order to develop an appropriate shared stepwise approach.
Topics: Humans; Extremities; Fibromatosis, Aggressive; Prospective Studies; Surgeons
PubMed: 37391208
DOI: 10.1302/0301-620X.105B7.BJJ-2023-0117 -
Oral and Maxillofacial Surgery Clinics... May 2024Craniofacial fibro-osseous lesions represent a diverse spectrum of pathologic conditions where fibrous tissue replaces healthy bone, resulting in the formation of... (Review)
Review
Craniofacial fibro-osseous lesions represent a diverse spectrum of pathologic conditions where fibrous tissue replaces healthy bone, resulting in the formation of irregular, woven bone. They are more commonly diagnosed in young people, with treatment strategies dependent on clinical behavior and skeletal maturity. This article discusses the examples of craniofacial fibro-osseous lesions, based on the latest classifications, along with their diagnostic criteria and management.
PubMed: 38705816
DOI: 10.1016/j.coms.2024.03.004 -
Journal of Oral and Maxillofacial... 2023Fibrolipoma, a subtype of lipoma, is a painless, well-circumscribed, slow-growing, submucosal benign adipocyte tumour. It is uncommon in the oral cavity and...
Fibrolipoma, a subtype of lipoma, is a painless, well-circumscribed, slow-growing, submucosal benign adipocyte tumour. It is uncommon in the oral cavity and oropharyngeal region. It accounts for 1.6% of all facial lipomas. Fibrolipomas mostly affect the buccal mucosa and buccal vestibule and cause functional and cosmetic disabilities. The diagnosis and differentiation of fibrolipoma with clinically similar lesions such as fibroma and pleomorphic adenoma are very essential for a correct treatment plan and complete follow-up. Here, we present fibrolipoma, a very rare subtype of lipoma involving the buccal mucosa of the left premolar region in a 44-year-old male patient.
PubMed: 38033946
DOI: 10.4103/jomfp.jomfp_105_23 -
The Journal of Hand Surgery Aug 2023Dupuytren disease is a benign, progressive fibroproliferative disorder of the hands. To date, only one pharmacotherapy (clostridial collagenase) has been approved for... (Review)
Review
Dupuytren disease is a benign, progressive fibroproliferative disorder of the hands. To date, only one pharmacotherapy (clostridial collagenase) has been approved for use in Dupuytren disease. There is a great need for additional nonsurgical methods that can be used to either avoid the risks of invasive treatments or help minimize recurrence rates following treatment. A number of nonsurgical modalities have been discussed in the past and continue to appear in discussions among hand surgeons, despite highly variable and often poor or no long-term clinical data. This article reviews many of the pharmacotherapies discussed in the treatment of Dupuytren disease and novel therapies used in inflammation and fibrosis that offer potential treatment options.
Topics: Humans; Dupuytren Contracture; Microbial Collagenase; Treatment Outcome; Injections, Intralesional; Clostridium histolyticum
PubMed: 36935324
DOI: 10.1016/j.jhsa.2023.02.003 -
Acta Chirurgiae Plasticae 2023This paper describes the evaluation options of Dupuytren's contracture by subjective and objective methods. There are various classification schemes named after their... (Review)
Review
This paper describes the evaluation options of Dupuytren's contracture by subjective and objective methods. There are various classification schemes named after their authors, including graphical representation for objective evaluation of the disease. Subjective assessment was performed in the form of a questionnaire for patients. The QuickDASH with a small specification for Dupuytren's contracture is the most commonly used questionnaire. The Southampton Dupuytren's Scoring Scheme questionnaire appears to be a higher specification. The classifications allow evaluation of treatment success to determine prognosis of the disease. The analysis of articles is based on PubMed search from the years 1967-2022, with 28 relevant articles were retrieved. Based on this analysis, the Tubiana classification appears to be the most appropriate one for patients with Dupuytren's contracture. Of patient questionnaires, the Southampton Dupuytren's Scoring Scheme meets these parameters.
Topics: Humans; Dupuytren Contracture; PubMed
PubMed: 37722904
DOI: 10.48095/ccachp202374