Tumour necrosis factor-α and apoptosis in the rat temporomandibular joint

Spears, Robert; Oakes, R. G.; Bellinger, Larry L.; Hutchins, Bob

doi:10.1016/s0003-9969(03)00175-4

Cited by 15 publications

(15 citation statements)

References 58 publications

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“…Indeed, Cyt are key mediators of CFA-induced arthritis. Their concentration and expression are significantly elevated in serum (26) and joint tissues (present results) of CFA-injected rats, respectively, and IL-1 antagonists and TNF-α-neutralizing antibodies reduce disease severity in these animals (51,52). We propose that PRL protects against CFA-induced inflammatory arthritis by reducing Cyt levels and counteracting their proapoptotic and proinflammatory actions on synovial cells, cartilage, and bone.…”

Section: Discussionsupporting

confidence: 51%

Prolactin promotes cartilage survival and attenuates inflammation in inflammatory arthritis

et al. 2013

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Chondrocytes are the only cells in cartilage, and their death by apoptosis contributes to cartilage loss in inflammatory joint diseases, such as rheumatoid arthritis (RA). A putative therapeutic intervention for RA is the inhibition of apoptosis-mediated cartilage degradation. The hormone prolactin (PRL) frequently increases in the circulation of patients with RA, but the role of hyperprolactinemia in disease activity is unclear. Here, we demonstrate that PRL inhibits the apoptosis of cultured chondrocytes in response to a mixture of proinflammatory cytokines (TNF-α, IL-1β, and IFN-γ) by preventing the induction of p53 and decreasing the BAX/BCL-2 ratio through a NO-independent, JAK2/STAT3-dependent pathway. Local treatment with PRL or increasing PRL circulating levels also prevented chondrocyte apoptosis evoked by injecting cytokines into the knee joints of rats, whereas the proapoptotic effect of cytokines was enhanced in PRL receptor-null (Prlr -/-) mice. Moreover, eliciting hyperprolactinemia in rats before or after inducing the adjuvant model of inflammatory arthritis reduced chondrocyte apoptosis, proinflammatory cytokine expression, pannus formation, bone erosion, joint swelling, and pain. These results reveal the protective effect of PRL against inflammation-induced chondrocyte apoptosis and the therapeutic potential of hyperprolactinemia to reduce permanent joint damage and inflammation in RA.

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Section: Discussionsupporting

confidence: 51%

Prolactin promotes cartilage survival and attenuates inflammation in inflammatory arthritis

et al. 2013

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“…Since apoptosis, or programmed cell death, is known to be responsible for tissue degeneration correlated with the severity of condyle and glenoid fossa pathologic processes [19,20], we determined if there was any alteration in cell apoptosis in the TMJ by TUNEL assay. Indeed, our results demonstrate a dramatically increased number of apoptotic cells in the glenoid fossa of Wnt1-Cre ; pMes-stop Shox2 TMJ compared to that in the wild type at P0 ( n = 3) (Figure 5C,D,M), indicating a contribution of apoptosis to the glenoid fossa dysplasia in Wnt1-Cre ; pMes-stop Shox2 mice.…”

Section: Resultsmentioning

confidence: 99%

Overexpression of Shox2 Leads to Congenital Dysplasia of the Temporomandibular Joint in Mice

Liang

et al. 2014

IJMS

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Our previous study reported that inactivation of Shox2 led to dysplasia and ankylosis of the temporomandibular joint (TMJ), and that replacing Shox2 with human Shox partially rescued the phenotype with a prematurely worn out articular disc. However, the mechanisms of Shox2 activity in TMJ development remain to be elucidated. In this study, we investigated the molecular and cellular basis for the congenital dysplasia of TMJ in Wnt1-Cre; pMes-stop Shox2 mice. We found that condyle and glenoid fossa dysplasia occurs primarily in the second week after the birth. The dysplastic TMJ of Wnt1-Cre; pMes-stop Shox2 mice exhibits a loss of Collagen type I, Collagen type II, Ihh and Gli2. In situ zymography and immunohistochemistry further demonstrate an up-regulation of matrix metalloproteinases (MMPs), MMP9 and MMP13, accompanied by a significantly increased cell apoptosis. In addition, the cell proliferation and expressions of Sox9, Runx2 and Ihh are no different in the embryonic TMJ between the wild type and mutant mice. Our results show that overexpression of Shox2 leads to the loss of extracellular matrix and the increase of cell apoptosis in TMJ dysplasia by up-regulating MMPs and down-regulating the Ihh signaling pathway.

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“…Behavioral hypersensitivity re-occurred weeks after gastrointestinal inflammation only in TNFR1/R2−/− mice while WT animals fully recovered from both insults. The use of CFA to model RA as well as persistent TMJ inflammation is well established, inducing edema in the joint and behavioral hypersensitivity (Spears et al, 2003), symptoms similar to clinical patients (Arthritis Foundation, http://www.arthritis.org). On a technical note, similar to a previous study, we tested the area over the TMJ with von Frey filaments (do Val et al, 2014).…”

Section: Discussionmentioning

confidence: 99%

Inflammatory ‘double hit’ model of temporomandibular joint disorder with elevated CCL2, CXCL9, CXCL10, RANTES and behavioural hypersensitivity in TNFR1/R2−/− mice

McIlwrath

Nesemeier

et al. 2017

European Journal of Pain

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Background Patients with temporomandibular joint disorders (TMD), reactive arthritis, and rheumatoid arthritis often have combined etiology of hereditary and microenvironmental factors contributing to joint pain. Multiple clinical and animal studies indicate “double-hit” inflammatory insults can cause chronic inflammation. The first inflammatory insult primes the immune system and subsequent insults elicit amplified responses. The present “double hit” study produced a chronic orofacial pain model in mice with genetic deletion of both TNFα receptors (TNFR1/R2−/−), investigating the main nociceptive signaling pathways in comparisons to wild type mice. Methods An initial inflammatory insult was given unilaterally into the temporomandibular joint (TMJ). Secondary hypersensitivity was tested on the skin over the TMJ throughout the experiment. Three weeks later after complete reversal of hypersensitivity, a second inflammatory insult was imposed on the colon. Pharmacological interventions were tested for efficacy after week 10 when hypersensitivity was chronic in TNFR1/R2−/− mice. Serum cytokines were analyzed Days 1, 14, and Week 18. Results The double hit insult produced chronic hypersensitivity continuing through the four month experimental timeline in the absence of TNFα signaling. P2X7 and NMDA receptor antagonists temporarily attenuated chronic hypersensitivity. Serum cytokine/chemokine analysis on Day 14 when CFA induced hypersensitivity was resolved identified increased levels of pro-inflammatory cytokines CCL2, CXCL9, CXCL10, RANTES and decreased levels of anti-inflammatory cytokines IL-1ra and IL-4 in TNFR1/R2−/− compared to WT mice. Conclusions These data suggest a causal feed-forward signaling cascade of these little studied cytokines have the potential to cause recrudescence in this orofacial inflammatory pain model in the absence of TNFα signaling.

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Tumour necrosis factor-α and apoptosis in the rat temporomandibular joint

Cited by 15 publications

References 58 publications

Prolactin promotes cartilage survival and attenuates inflammation in inflammatory arthritis

Prolactin promotes cartilage survival and attenuates inflammation in inflammatory arthritis

Overexpression of Shox2 Leads to Congenital Dysplasia of the Temporomandibular Joint in Mice

Inflammatory ‘double hit’ model of temporomandibular joint disorder with elevated CCL2, CXCL9, CXCL10, RANTES and behavioural hypersensitivity in TNFR1/R2−/− mice

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