The substance P fragment SP-(7-11) increases prostaglandin E2, intracellular Ca2+ and collagenase production in bovine articular chondrocytes

Halliday, Dale; McNeil, Julian; Betts, W H; Scicchitano, R.

doi:10.1042/bj2920057

Cited by 17 publications

(10 citation statements)

References 45 publications

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“…Several reports have suggested an association between cartilaginous tissue and neuropeptides, such as substance P, a calcitonin gene‐related peptide in vitro (Halliday et al. 1993; Edoff & Hildebrand, 2003).…”

Section: Discussionmentioning

confidence: 99%

Expression of Ten‐m/Odz3 in the fibrous layer of mandibular condylar cartilage during postnatal growth in mice

et al. 2010

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It has been speculated that the mandibular condyle develops via the differentiation of the fibroblast-like cells covering the condyle into chondrocytes; however, the developmental mechanisms behind this process have not been revealed. We used laser-capture microdissection and cDNA microarray analysis to elucidate the genes that are highly expressed in these fibroblast-like cells. Among these genes, the transcription of Ten-m ⁄ Odz3 was significantly increased in the fibroblast-like cells compared with other cartilage tissues. For the first time, we describe the temporal and spatial expression of Ten-m ⁄ Odz3 mRNA in relation to the expression of type I, II, and X collagen mRNA, as determined by in-situ hybridization in mouse mandibular condylar cartilage and mouse femoral cartilage during the early stages of development. Ten-m ⁄ Odz3 was expressed in the fibrous layer and the proliferating and mature chondrocyte layers, which expressed type I and II collagen, respectively, but was not detected in the hypertrophic chondrocyte layer. Furthermore, we evaluated the in-vitro expression of Ten-m ⁄ Odz3 using ATDC5 cells, a mouse chondrogenic cell line. Ten-m ⁄ Odz3 was expressed during the early stage of the differentiation of mesenchymal cells into chondrocytes. These findings suggest that Ten-m ⁄ Odz3 is involved in the differentiation of chondrocytes and that it acts as a regulatory factor in the early stages of the development of mandibular condylar cartilage.

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Section: Discussionmentioning

confidence: 99%

Expression of Ten‐m/Odz3 in the fibrous layer of mandibular condylar cartilage during postnatal growth in mice

et al. 2010

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“…The presence of neuropeptides, especially substance P, has been demonstrated in OA tissues (45). Substance P was demonstrated to increase the level of intracellular Ca 2+ as well as the synthesis of cytokines and MMPs by cartilage chondrocytes (46). The action of PD‐0200347 at the Ca 2+ channel level could very well explain how it inhibits the action of substance P (47).…”

Section: Discussionmentioning

confidence: 99%

Oral treatment with PD‐0200347, an α₂δ ligand, reduces the development of experimental osteoarthritis by inhibiting metalloproteinases and inducible nitric oxide synthase gene expression and synthesis in cartilage chondrocytes

Boileau¹,

Martel‐Pelletier²,

Brunet³

et al. 2005

Arthritis & Rheumatism

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Objective. To examine the in vivo effects of PD-0200347, an ␣ 2 ␦ ligand of voltage-activated Ca 2؉ channels and a compound chemically related to pregabalin and gabapentin, on the development of cartilage structural changes in an experimental dog model of osteoarthritis (OA). The effects of PD-0200347 on the major pathways involved in OA cartilage degradation, including matrix metalloproteinases (MMPs) and the inducible form of nitric oxide synthase (iNOS), were also studied.Methods. OA was surgically induced in dogs by sectioning the anterior cruciate ligament. OA dogs were randomly distributed into 3 groups and treated orally with either 1) placebo, 2) 15 mg/kg/day of PD-0200347, or 3) 90 mg/kg/day of PD-0200347. Dogs were killed 12 weeks after surgery. The severity of the lesions was scored macroscopically and histologically. Cartilage specimens from the femoral condyles and tibial plateaus were processed for RNA extraction and quantitative reverse transcription-polymerase chain reaction (RT-PCR) or immunohistochemistry. Specific probes and antibodies were used to study the messenger RNA and protein levels of iNOS, MMP-1, MMP-3, and MMP-13.Results. No clinical signs of drug toxicity were noted in the treated animals. Treatment with PD-0200347 at both dosages tested (15 and 90 mg/kg/day) reduced the development of cartilage lesions. There was a reduction in the score of lesions, with a statistically significant (P ‫؍‬ 0.01) difference when the highest dosage of the drug was administered. The reduction in the score was mainly related to a decrease in the surface size of the lesions. Quantitative RT-PCR showed that PD-0200347 significantly reduced the expression of MMP-13, a key mediator in OA. Immunohistochemical analyses showed that treatment with PD-0200347 significantly reduced the synthesis of all key OA mediators studied.Conclusion. This study demonstrated the efficacy of PD-0200347 in reducing the progression of cartilage structural changes in a dog model of OA. It also showed that this effect is linked to the inhibition of the major pathophysiologic mediators responsible for cartilage degradation.

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“…The quantification of CT-induced changes in intracellular calcium was performed as described previously (Halliday et al 1993). Cells were grown in a 75 cm 2 culture flask until confluent, trypsinised and resuspended in serum-depleted DMEM containing 1·0 µM Fura-2AM (Calbiochem, La Jolla, CA, USA).…”

Section: Intracellular Calcium Assaymentioning

confidence: 99%

Sustained activation of Erk1/2 MAPK and cell growth suppression by the insert-negative, but not the insert-positive isoform of the human calcitonin receptor

Raggatt

Evdokiou²,

Findlay³

2000

Journal of Endocrinology

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Recently we reported that calcitonin (CT) induces growth arrest at the G2 stage of the cell cycle in HEK-293 cell lines expressing the most abundant, insert-negative, isoform of the human CT receptor (insert ve hCTR). The present study investigates the involvement of the MAPK signalling pathway in the anti-proliferative actions of CT and compares the activity of an isoform of the hCTR that contains a 16 amino acid insert in the first putative intracellular loop (insert +ve hCTR). Comparison of HEK-293 cells stably transfected with the insert ve or the insert +ve hCTR, showed that accumulation of cAMP and intracellular free calcium in response to CT were specific for the insert ve receptor isoform. However, a novel acidification of the extracellular medium was mediated by both isoforms. Treatment with CT of cells expressing the insert ve hCTR, caused a decrease in cell growth associated with an induction of p21 WAF1/CIP1 . Analysis by fluorescence-activated cell scanning showed that growth inhibition was associated with an accumulation of cells in G2. CT treatment of cells expressing the insert ve, but not insert +ve hCTR, induced the phosphorylation of Erk1/2 MAPK, which persisted for at least 72 h. Treatment of cells expressing the insert ve hCTR with the MAPK kinase (MEK) inhibitor, PD-98059, inhibited the phosphorylation of Erk1/2 and abrogated the growth inhibitory effects of salmon CT, the accumulation of cells in G2, and the associated induction of p21 WAF1/CIP1 . These data suggest that activation of Erk1/2 are downstream effectors of the insert ve hCTR in modulating cell cycle progression.

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The substance P fragment SP-(7-11) increases prostaglandin E2, intracellular Ca2+ and collagenase production in bovine articular chondrocytes

Cited by 17 publications

References 45 publications

Expression of Ten‐m/Odz3 in the fibrous layer of mandibular condylar cartilage during postnatal growth in mice

Expression of Ten‐m/Odz3 in the fibrous layer of mandibular condylar cartilage during postnatal growth in mice

Oral treatment with PD‐0200347, an α₂δ ligand, reduces the development of experimental osteoarthritis by inhibiting metalloproteinases and inducible nitric oxide synthase gene expression and synthesis in cartilage chondrocytes

Sustained activation of Erk1/2 MAPK and cell growth suppression by the insert-negative, but not the insert-positive isoform of the human calcitonin receptor

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The substance P fragment SP-(7-11) increases prostaglandin E2, intracellular Ca2+ and collagenase production in bovine articular chondrocytes

Cited by 17 publications

References 45 publications

Expression of Ten‐m/Odz3 in the fibrous layer of mandibular condylar cartilage during postnatal growth in mice

Expression of Ten‐m/Odz3 in the fibrous layer of mandibular condylar cartilage during postnatal growth in mice

Oral treatment with PD‐0200347, an α2δ ligand, reduces the development of experimental osteoarthritis by inhibiting metalloproteinases and inducible nitric oxide synthase gene expression and synthesis in cartilage chondrocytes

Sustained activation of Erk1/2 MAPK and cell growth suppression by the insert-negative, but not the insert-positive isoform of the human calcitonin receptor

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Oral treatment with PD‐0200347, an α₂δ ligand, reduces the development of experimental osteoarthritis by inhibiting metalloproteinases and inducible nitric oxide synthase gene expression and synthesis in cartilage chondrocytes