Different mechanisms of synovial hyperplasia in rheumatoid arthritis and pigmented villonodular synovitis: The role of telomerase activity in synovial proliferation

Yudoh, Kazuo; Matsuno, Hiroaki; Nezuka, T.; Kimura, Takeshi

doi:10.1002/1529-0131(199904)42:4<669::aid-anr9>3.0.co;2-v

Cited by 40 publications

(23 citation statements)

References 33 publications

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“…Activation of telomerase is well known to be associated not only with carcinogenesis, but also with apoptosis. Recently, both synovial proliferation in RA (35) and increased disease activity in SLE (36) have been shown to be associated with increased telomerase activity.…”

Section: Discussionsupporting

confidence: 67%

Stratification of pedigrees multiplex for systemic lupus erythematosus and for self‐reported rheumatoid arthritis detects a systemic lupus erythematosus susceptibility gene (SLER1) at 5p15.3

Namjou

Nath

Kilpatrick

et al. 2002

Arthritis & Rheumatism

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Objective. Arthritis is a common manifestation in systemic lupus erythematosus (SLE), appearing in ϳ85% of patients. Often, the polyarthritis at presentation of SLE cannot be distinguished from rheumatoid arthritis (RA) by physical examination or history. Indeed, physicians initially tell many SLE patients that they have RA (one source of "self-reported RA"), only to have SLE established later. In addition, RA aggregates in families with an SLE proband. We predicted that pedigrees multiplex for both SLE and for self-reported RA would better isolate particular genetic effects. If this proved to be true, we would then use the increased genetic homogeneity to more easily reveal genetic linkage.Methods. From a collection of 160 pedigrees multiplex for SLE, we selected 36 pedigrees that also contained >2 members with self-reported RA (19 pedigrees were African American, 14 were European American, and 3 were of other ethnic origin). Data from a genome scan of 307 microsatellite markers were evaluated for SLE linkage by contemporary genetic epidemiologic techniques.Results. The most significant evidence of linkage to SLE was obtained at 5p15.3 in the European American pedigrees by both parametric (logarithm of odds [LOD] score 6.2, P ‫؍‬ 9.3 ؋ 10 ؊8) and nonparametric (LOD score 6.9, P ‫؍‬ 1.7 ؋ 10 ؊8 ) methods. The bestfitting model for this putative SLE gene in this region was a recessive gene with a population frequency of 5% and with 50% penetrance in females and 15% penetrance in males at virtually 100% homogeneity.Conclusion. For a genetically complex disease phenotype, an unusually powerful linkage has been found with SLE at 5p15.3 in European American pedigrees multiplex for SLE and for self-reported RA. This result predicts the presence of a gene at the top of chromosome 5 in this subset of patients that is important for the pathogenesis of SLE.Strong evidence exists for a genetic component in systemic lupus erythematosus (SLE). Familial aggregation, high sibling recurrence rates ( s ϭ 10-40) (1), increased monozygotic twin concordance rates compared with those for dizygotic twins and other full siblings (2), and the discovery of genetic linkages and associations all support the existence of susceptibility genes for SLE. Indeed, a number of genetic associations have been clearly established with SLE. Examples include alleles at multiple genes in the HLA region, including HLA-DR3 and various complement components, and the Fc␥ region of 1q23.1 (3-5). More recent investigations have also established multiple genetic linkages with SLE, including effects at 1q21. 3, 1q41, 2q37, 4p16, 6p21, and 16q13 (6-8).Rheumatoid arthritis (RA) is related to SLE on

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Section: Discussionsupporting

confidence: 67%

Stratification of pedigrees multiplex for systemic lupus erythematosus and for self‐reported rheumatoid arthritis detects a systemic lupus erythematosus susceptibility gene (SLER1) at 5p15.3

Namjou

Nath

Kilpatrick

et al. 2002

Arthritis & Rheumatism

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“…The pathologic mechanism for growth of hypertrophic villi in PVNS is different from synovial growth in RA. Synovial hyperplasia in PVNS might be due to upregulation of synoviocyte proliferation as represented by activation of telomerase, which is evident in the majority of tumor cell lines [15]. That is why the treatment such as with TNF-alpha blockade did not reduce synovial tumor mass as measured by MRI but alleviated and stabilized synovial inflammation and joint effusion [13,14].…”

Section: Discussionsupporting

confidence: 91%

Pigmented Villonodular Synovitis for Combined Therapy

Rozin

2014

J Med Cases

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Pigmented villonodular synovitis (PVNS), inflammatory proliferative disease resulting from synovial cells, has progressive course similar neoplastic local expansion. We followed up a case with effective combined therapy for diffuse PVNS despite incomplete response to its components and reviewed therapies based on MedLine for PVNS. Due to US data residue synovitis after open radical synovectomy, we made decision about external beam radiotherapy. Photon radiation with linear accelerator energy of 6 MV was applied for two fields: anterior and posterior. The total dose was 20 Gy, delivered in 2 Gy a day, five times a week. Due to postoperative pain and the rest of synovial tissue on US study, pharmacologic therapy with salazopyrine and celecoxib was added. For several weeks, the knee pain became episodic and further disappeared. Six months later, the patient feels healthy and continues to take salazopyrine permanently and celecoxib as needed. We conclude high rate response analyzing literature data and our case to combined therapy: arthroscopic or open surgery followed by RT along with complimentary pharmacotherapy.

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“…Accordingly, the intracellular pathways through which FLSC activities are regulated have become a subject of increasing interest. Signaling and/or regulatory molecules implicated in the proliferative and/or degradative activities of FLSCs include the mitogen-activated protein kinases (MAPKs) c-Jun N-terminal kinase (JNK) and p38 (9,10), the tumor suppressor p53 (11,12), the proinflammatory transcription factor NF-B (13), and possibly telomerase (14). However, the precise role of each of these in inflammatory joint destruction remains to be fully elucidated.…”

mentioning

confidence: 99%

Cyclooxygenase-2-Derived E Prostaglandins Down-Regulate Matrix Metalloproteinase-1 Expression in Fibroblast-Like Synoviocytes via Inhibition of Extracellular Signal-Regulated Kinase Activation

Pillinger

Rosenthal

Tolani

et al. 2003

The Journal of Immunology

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We examined the regulation of matrix metalloproteinase (MMP) production by mitogen-activated protein kinases and cyclooxygenases (COXs) in fibroblast-like synoviocytes (FLSCs). IL-1β and TNF-α stimulated FLSC extracellular signal-regulated kinase (ERK) activation as well as MMP-1 and -13 release. Pharmacologic inhibitors of ERK inhibited MMP-1, but not MMP-13 expression. Whereas millimolar salicylates inhibited both ERK and MMP-1, nonsalicylate COX and selective COX-2 inhibitors enhanced stimulated MMP-1 release. Addition of exogenous PGE1 or PGE2 inhibited MMP-1, reversed the effects of COX inhibitors, and inhibited ERK activation, suggesting that COX-2 activity tonically inhibits MMP-1 production via ERK inhibition by E PGs. Exposure of FLSCs to nonselective COX and selective COX-2 inhibitors in the absence of stimulation resulted in up-regulation of MMP-1 expression in an ERK-dependent manner. Moreover, COX inhibition sufficient to reduce PGE levels increased ERK activity. Our data indicate that: 1) ERK activation mediates MMP-1 but not MMP-13 release from FLSCs, 2) COX-2-derived E PGs inhibit MMP-1 release from FLSCs via inhibition of ERK, and 3) COX inhibitors, by attenuating PGE inhibition of ERK, enhance the release of MMP-1 by FLSC.

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Different mechanisms of synovial hyperplasia in rheumatoid arthritis and pigmented villonodular synovitis: The role of telomerase activity in synovial proliferation

Abstract: Telomerase activation in lymphocytes may provide insights into the progression of synovitis and synovial proliferation in RA. Moreover, the enzyme may be implicated in the proliferation of synoviocytes in PVS.

Cited by 40 publications

References 33 publications

Stratification of pedigrees multiplex for systemic lupus erythematosus and for self‐reported rheumatoid arthritis detects a systemic lupus erythematosus susceptibility gene (SLER1) at 5p15.3

Stratification of pedigrees multiplex for systemic lupus erythematosus and for self‐reported rheumatoid arthritis detects a systemic lupus erythematosus susceptibility gene (SLER1) at 5p15.3

Pigmented Villonodular Synovitis for Combined Therapy

Cyclooxygenase-2-Derived E Prostaglandins Down-Regulate Matrix Metalloproteinase-1 Expression in Fibroblast-Like Synoviocytes via Inhibition of Extracellular Signal-Regulated Kinase Activation

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