Stimulation of cartilage resorption by extracellular ATP acting at P2-purinoceptors

Ws, Leong; Russell, R. G. G.; Caswell, Amanda

doi:10.1016/0304-4165(94)90054-x

Cited by 52 publications

(37 citation statements)

References 36 publications

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“…First, it has been noted that macrophage-secreted cytokines drive cartilage resorption. Thus, fresh autologous cartilage grafts would be exposed to an environment of macrophage-mediated wound healing, leading to a loss of the extracellular matrix from the cartilage [Leong et al, 1994;Rainsford, 1989;Tjelmeland and Stal, 2000]. In an animal study by Elwany et al [2006], the perichondrium was found to act as a protective barrier that prevented the direct exposure of the graft to the deleterious effects of the local mediators of the woundhealing environment.…”

Section: Discussionmentioning

confidence: 99%

Mastoid Obliteration for Pediatric Suppurative Cholesteatoma: Long-Term Safety and Sustained Effectiveness after 30 Years' Experience with Cartilage Obliteration

Kuo

Lien²,

Shiao³

2014

Audiol Neurotol

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Objective: To analyze the long-term safety of mastoid obliteration with cartilage in children with suppurative cholesteatomatous ears. Methods: The medical records of children (≤18 years) with cholesteatomas after primary tympanomastoidectomies were performed with cartilage obliteration over a 30-year period (1982-2012) were analyzed. The recidivism rate was calculated using the Kaplan-Meier survival analysis. Potentially confounding factors of recidivism were entered into a Cox regression model as covariates for multivariate analysis. Results: Of the 150 cholesteatomatous ears in 146 children, there were 95 discharging ears (63%) in 94 children. Among the 95 discharging ears, tympanomastoidectomy was performed with cartilage obliteration (CO group) in 77 ears (81%) and without cartilage obliteration (WO group) in 18 ears (19%). The mean follow-up period was 12 years. Recidivism was observed in 16 ears in the CO group and 4 ears in the WO group. The 10-year cumulative recidivism rates were comparable between the CO and WO groups (19 vs. 25%, p = 0.762). Multivariate analysis confirmed that mastoid obliteration was not a negative predictor of recidivism (p = 0.760). Recidivism of cholesteatoma was detected within 6.5 years after surgery in the WO group and was found as late as 16.1 years after surgery in the CO group. Cartilage could be maintained in the cavity with limited resorption, preventing reretraction pockets and subsequent recidivism. Conclusion: This study provides evidence supporting the long-term safety, feasibility and effectiveness of mastoid cartilage obliteration for children with suppurative cholesteatomatous ears. Despite comparable recidivism rates between the groups, the potential for the delayed detection of recidivism with cavity obliteration may warrant long-term follow-up, with careful attention paid to the potential for recidivism during postoperative care in children. i 2014 S. Karger AG, Basel

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Section: Discussionmentioning

confidence: 99%

Mastoid Obliteration for Pediatric Suppurative Cholesteatoma: Long-Term Safety and Sustained Effectiveness after 30 Years' Experience with Cartilage Obliteration

Kuo

Lien²,

Shiao³

2014

Audiol Neurotol

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“…This is supported by the finding that the synovial fluids of patients affected by OA or RA contain high concentrations of ATP (6). Leong et al (7,8) reported that ATP triggered the degradation of cultured explants of bovine nasal cartilage and stimulated PGE 2 production by articular chondrocytes. IL-1␤ and TNF-␣ both interact synergistically with extracellular ATP (9,10).…”

mentioning

confidence: 99%

Concomitant Recruitment of ERK1/2 and p38 MAPK Signalling Pathway Is Required for Activation of Cytoplasmic Phospholipase A2via ATP in Articular Chondrocytes

Bérenbaum¹,

Humbert²,

Béréziat³

et al. 2003

Journal of Biological Chemistry

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Extracellular ATP is a pro-inflammatory mediator involved in the release of prostaglandin from articular chondrocytes, but little is known about its effects on intracellular signaling. ATP triggered the rapid release of prostaglandin E 2 (PGE 2 ) by acting on P2Y 2 receptors in rabbit articular chondrocytes. We have explored the signaling events involved in this synthesis. ATP significantly increased arachidonic acid production, which involved the activation of the 85-kDa cytosolic phospholipase A 2 (cPLA 2 ) but not a secreted form of PLA 2 , as demonstrated by various PLA 2 inhibitors and translocation experiments. We also showed that ATP induced the phosphorylation of p38 and ERK1/2 mitogen-activatedprotein kinases (MAPKs). Both PD98059, an inhibitor of the ERK pathway, and SB203580, an inhibitor of p38 MAPK, completely inhibited the ATP-induced release of PGE 2 . Finally, dominant-negative plasmids encoding p38 and ERK transfected alone into the cells impaired the ATP-induced release of PGE 2 to about the same extent as both plasmids transfected together. These results suggest that PGE 2 production induced by ATP requires the activation of both ERK1/2 and p38 MAPKs. Thus, ATP acts via P2Y 2 -purine receptors to recruit cPLA 2 by activating both ERK1/2 and p38 MAPKs and stimulates the release of PGE 2 from articular chondrocytes.

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“…The response of human articular chondrocytes to ATP is enhanced by IL-1β [297] and TNF-α [318,319]. Activation of P2Y receptors also leads to elevated fibroblast growth factor-induced proliferation [298,299].…”

Section: P2 Receptor Expression By Chondrocytesmentioning

confidence: 99%

Purinergic signalling in the musculoskeletal system

Burnstock

Arnett

Orriss

2013

Purinergic Signalling

111

114

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It is now widely recognised that extracellular nucleotides, signalling via purinergic receptors, participate in numerous biological processes in most tissues. It has become evident that extracellular nucleotides have significant regulatory effects in the musculoskeletal system. In early development, ATP released from motor nerves along with acetylcholine acts as a cotransmitter in neuromuscular transmission; in mature animals, ATP functions as a neuromodulator. Purinergic receptors expressed by skeletal muscle and satellite cells play important pathophysiological roles in their development or repair. In many cell types, expression of purinergic receptors is often dependent on differentiation. For example, sequential expression of P2X5, P2Y 1 and P2X2 receptors occurs during muscle regeneration in the mdx model of muscular dystrophy. In bone and cartilage cells, the functional effects of purinergic signalling appear to be largely negative. ATP stimulates the formation and activation of osteoclasts, the bone-destroying cells. Another role appears to be as a potent local inhibitor of mineralisation. In osteoblasts, the bone-forming cells, ATP acts via P2 receptors to limit bone mineralisation by inhibiting alkaline phosphatase expression and activity. Extracellular ATP additionally exerts significant effects on mineralisation via its hydrolysis product, pyrophosphate. Evidence now suggests that purinergic signalling is potentially important in several bone and joint disorders including osteoporosis, rheumatoid arthritis and cancers. Strategies for future musculoskeletal therapies might involve modulation of purinergic receptor function or of the ecto-nucleotidases responsible for ATP breakdown or ATP transport inhibitors.

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Stimulation of cartilage resorption by extracellular ATP acting at P2-purinoceptors

Cited by 52 publications

References 36 publications

Mastoid Obliteration for Pediatric Suppurative Cholesteatoma: Long-Term Safety and Sustained Effectiveness after 30 Years' Experience with Cartilage Obliteration

Mastoid Obliteration for Pediatric Suppurative Cholesteatoma: Long-Term Safety and Sustained Effectiveness after 30 Years' Experience with Cartilage Obliteration

Concomitant Recruitment of ERK1/2 and p38 MAPK Signalling Pathway Is Required for Activation of Cytoplasmic Phospholipase A2via ATP in Articular Chondrocytes

Purinergic signalling in the musculoskeletal system

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