Objective: Pigmented villonodular synovitis (PVNS) is a rare benign proliferative disease affecting the soft-tissue lining the synovial joints and tendons. Its etiology is poorly understood, largely limiting the availability of current therapeutic options. Here, we mapped the synovial gene and protein profiles of patients with PVNS, revealed a link between synovial inflammation and invasion, and elucidated the potential molecular mechanism involved.
Methods: The expression of synovial genes from 6 control individuals, 7 patients with osteoarthritis (OA), and 19 patients with PVNS was analyzed via RNA sequencing. Protein profiles from 5 control individuals, 10 patients with OA, and 32 patients with PVNS were analyzed using label-free proteomics. Microarray and reverse transcription-polymerase chain reaction analyses and immunohistochemical staining were used to evaluate inflammatory cytokine and target gene expression levels in synovial tissue, epithelial cells, and synovial fibroblasts (FLSs) derived from tissue of patients with PVNS. Various signaling pathway inhibitors, small interfering RNAs, and Western blots were used for molecular mechanism studies. Transwell migration and invasion assays were subsequently performed.
Results: In total, 522 differentially expressed proteins were identified in the tissues of patients with PVNS. By integrating RNA sequencing and microarray analyses, significant changes in the expression of epithelial-mesenchymal transition (EMT)-related genes, including transforming growth factor TGF-b induced, neural cadherin, epithelial cadherin, SNAIL, and TWIST, were confirmed in the tissue of patients with PVNS compared to the control tissue. In vitro, TGFβ induced EMT and increased epithelial cell migration and invasion. Moreover, TGFβ not only promoted interactions between epithelial cells and FLSs but also directly increased the migration and invasion abilities of FLSs by activating the classical Smad2/3 and nonclassical JNK/AKT signaling pathways.
Conclusion: This study provides overall protein and gene profiles of PVNS and identifies the crucial role of TGFβ in synovial invasion pathology. Exploring the related molecular mechanism may also reveal a new strategy or target for PVNS therapy.
Download full-text PDF |
Source |
---|---|
http://dx.doi.org/10.1002/art.42946 | DOI Listing |
J Orthop Case Rep
January 2025
Department of Orthopaedics, Bharatratna Dr. Babasaheb Ambedkar Municipal General Hospital, Mumbai, Maharashtra, India.
Introduction: A form of tenosynovial giant cell tumors (GCTs) that diffusely affects the soft tissue lining of joints and tendons is called pigmented villonodular synovitis or PVNS. About equal percentages of men and women are often affected, and it typically affects young individuals. The most typical sites of PVNS are the knee and ankle, making PVNS of the wrist a rare presentation.
View Article and Find Full Text PDFRev Bras Ortop (Sao Paulo)
November 2024
Serviço de Ortopedia e Traumatologia, Hospital Santa Rita de Cássia, Vitória, ES, Brasil.
Pigmented villonodular synovitis (PVNS) is rare in the shoulder, with few descriptions in the literature. We present the case of a 58-year-old female patient with no history of trauma. The patient reported pain for 2 months with no limb irradiation and presented lifting strength loss and progressive limitation of active and passive mobility.
View Article and Find Full Text PDFExpert Rev Anticancer Ther
December 2024
Department of Internal Medicine, Division of Hematology/Oncology, University of Michigan, Ann Arbor, MI, USA.
Cureus
November 2024
Orthopaedic Surgery, The University of Alabama at Birmingham, Birmingham, USA.
Pigmented villonodular synovitis (PVNS) is an uncommon hyperproliferative disease of the synovium presenting either as localized or a more aggressive diffuse form. Its occurrence following total knee arthroplasty (TKA) is rare, and its presentation alongside patellar clunk syndrome (PCS) has not been previously reported. We present a case of a 64-year-old female patient diagnosed with diffuse PVNS (D-PVNS) two and half years following TKA, co-occurring with PCS.
View Article and Find Full Text PDFJ Knee Surg
November 2024
Department of Orthopaedics, University of Maryland School of Medicine, Baltimore, Maryland.
Pigmented villonodular synovitis (PVNS) is a rare neoplastic proliferation of large joints, including the knee, with both localized PVNS (LPVNS) and diffuse PVNS (DPVNS) types. DPVNS is known to recur at a higher rate following resection; however, there is little evidence comparing patient-reported outcomes (PROs) between the two types. The purpose of this study was to compare PROs between patients with LPVNS and DPVNS involving the knee 2 years after surgical resection.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!