Molecular pathways involved in synovial cell inflammation and tumoral proliferation in diffuse pigmented villonodular synovitis

Fiocco, Ugo; Sfriso, Paolo; Lunardi, Francesca; Pagnin, Elisa; Oliviero, Francesca; Scagliori, Elena; Cozzi, L.; Vezzù, Maristella; Molena, Béatrice; Scanu, Anna; Panziera, C; Nardacchione, Roberto; Rubaltelli, Léopoldo; Jm, Dayer; Calabrese, Fiorella; Punzi, Leonardo

doi:10.1016/j.autrev.2010.07.001

Cited by 40 publications

(23 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This overexpression is responsible for a recruitment of inflammatory cells, within the tumour, expressing the receptor in CSF. 12 These results open the way for targeted therapies. The hypothesis of a lipid metabolic disorder associated with an anomaly of the local lipid metabolism is a possible aetiology.…”

Section: Aetiologymentioning

confidence: 96%

Pigmented villonodular synovitis of the hip

2016

View full text Add to dashboard Cite

Pigmented villonodular synovitis (PVNS) is a rare disease that can affect any joint, bursa or tendon sheath.The hip is less frequently affected than the knee, and hence is less discussed in scientific journals.PVNS of the hip mainly occurs in young adults, requiring early diagnosis and adequate treatment to obtain good results.There is no consensus on the management of PVNS of the hip in current literature.We will discuss the options for surgical intervention in hip PVNS using a literature review of clinical, biological, etiological, histological and radiographic aspects of the disease.Cite this article: Steinmetz S, Rougemont A-L, Peter R. Pigmented villonodular synovitis of the hip. EFORT Open Rev 2016;1:260-266. DOI: 10.1302/2058-5241.1.000021.

show abstract

Section: Aetiologymentioning

confidence: 96%

Pigmented villonodular synovitis of the hip

2016

View full text Add to dashboard Cite

show abstract

“…Although the etiology of PVNS is unclear at present, recent evidence suggests a neoplastic nature (6)(7)(8), and malignant cases have been reported (9,10). The disease, which can involve all synovial-lined structures, particularly the knee joint, is characterized by proliferation of synovial tissues and invasion of cartilage and bone around the joints.…”

Section: Introductionmentioning

confidence: 99%

Imatinib mesylate induces mitochondria-dependent apoptosis and inhibits invasion of human pigmented villonodular synovitis fibroblast-like synovial cells

et al. 2015

View full text Add to dashboard Cite

Pigmented villonodular synovitis (PVNS) is a rare sarcoma-like disorder characterized by synovial lesions proliferation and invasion to articular cartilage for which no effective treatments are available. Imatinib mesylate (IM) is known to exert antitumor activity in some tumors, but its effects on PVNS fibroblast-like synoviocytes (PVNS-FLS) and the specific mechanism involved remain to be established. In the present study, the in vitro effects of IM on cell proliferation and survival rates were investigated in PVNS-FLS. Apoptosis induction was assessed via acridine orange/ethidium bromide (AO)/(EB) and Annexin V/PI staining as well as western blotting. The invasion ability of PVNS-FLS was evaluated by Transwell invasion chambers. IM significantly inhibited survival and invasion ability of PVNS-FLS in a dose- and time-dependent manner. The drug-treated cell groups exhibited markedly higher apoptosis, which was blocked upon pretreatment with the specific caspase-9 inhibitor Z-LEHD-FMK. Expression of cleaved caspase-9 was significantly increased and the Bcl-2 family and caspase-3 were activated following treatment with IM. Our results collectively demonstrated that IM has a strong antiproliferative effect on PVNS-FLS in vitro, attributable to induction of mitochondrial-dependent apoptosis in association with activation of caspase-9/-3 and the Bcl-2/Bax family, and exhibits significant inhibition on the invasion ability of PVNS-FLS, suggesting that IM may be useful as a novel treatment of this disease.

show abstract

“…Macrophage fusion may lead to foreign body-type giant cells (FBGCs), osteoclast-type giant cells (OCGCs) or mycobacterium-induced Langhans-type giant cells (LHGCs), depending on the known or unknown inciting causes. A variety of molecules including ␤ 1-and ␤ 2-integrin receptor families, interleukin-4, vitronectin, E-cadherin, dendritic cell-specific transmembrane protein (DC-STAMP), P2X7 receptor, CD44 and connexin 43 have been identified as mediators of FBGC formation [5,6] , some of which have also been implicated as common molecules necessary for the multinucleation of both OCGCs and LHGCs [7][8][9] . However, little is known about the signals that drive multinucleated giant cell formation and maintenance, the molecular mechanism by which macrophage fusion occurs, or their physiological significance at sites of chronic inflammation.…”

Section: Introductionmentioning

confidence: 99%

Frequent Upregulation of Cyclin D1 and p16INK4a Expression with Low Ki-67 Scores in Multinucleated Giant Cells

Choi¹,

Lee²,

Kim³

2011

Pathobiology

View full text Add to dashboard Cite

Background/Aims: Multinucleated giant cells are formed from the fusion of macrophages and are classified into foreign body-type giant cells (FBGCs), osteoclast-type giant cells (OCGCs) and Langhans-type giant cells (LHGCs). OCGCs display upregulated cyclin D1 expression with low Ki-67 activity. However, little is known about the expression of cell cycle regulators in the other types of multinucleated giant cells. We aimed to investigate the cell cycle status of multinucleated giant cells. Methods: The immunohistochemical expressions of cyclin D1, p16^INK4a and Ki-67 were analyzed in a total of 127 cases showing multinucleated giant cells. Results: Cyclin D1 was overexpressed in 45 (88%) of 51 FBGC cases, 25 (86%) of 29 OCGC cases and 22 (47%) of 47 LHGC cases. p16^INK4a showed diffuse nuclear and/or cytoplasmic overexpression in 45 (88%) of 51 FBGC cases, 27 (93%) of 29 OCGC cases and 24 (51%) of 47 LHGC cases. Ki-67 immunostaining was negative in almost all FBGC, OCGC and LHGC cases. Conclusion: This study demonstrates that FBGCs and OCGCs frequently show upregulation of cyclin D1 and p16^INK4a expression with low Ki-67 scores. This suggests that multinucleated giant cells are arrested in the G1/S cell cycle transition.

show abstract

Molecular pathways involved in synovial cell inflammation and tumoral proliferation in diffuse pigmented villonodular synovitis

Cited by 40 publications

References 34 publications

Pigmented villonodular synovitis of the hip

Pigmented villonodular synovitis of the hip

Imatinib mesylate induces mitochondria-dependent apoptosis and inhibits invasion of human pigmented villonodular synovitis fibroblast-like synovial cells

Frequent Upregulation of Cyclin D1 and p16INK4a Expression with Low Ki-67 Scores in Multinucleated Giant Cells

Contact Info

Product

Resources

About