Expression of functional μ-opioid receptors in human osteoarthritic cartilage and chondrocytes

Elvenes, Jan; Andjelkov, Nenad; Figenschau, Yngve; Seternes, Tore; Bjørkøy, Geir; Johansen, Oddmund

doi:10.1016/j.bbrc.2003.09.191

Cited by 29 publications

(31 citation statements)

References 22 publications

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“…Simultaneously, it has been recently demonstrated by our group that β-END increase the IL-1β protein levels in human articular chondrocytes (2). There is no evidence that human articular chondrocytes produce β-END (1), but they can be affected by β-END via a µ-opioid receptor (9).…”

Section: Introductionmentioning

confidence: 99%

β-Endorphin Regulation of MAPKs in Cultured Human Articular Chondrocytes: MAPK Inhibitors Prevent the Increase of IL-1β Protein Levels During β-Endorphin Stimulation

Andjelkov¹,

Elvenes²,

Knutsen³

et al. 2007

Cell Communication & Adhesion

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We investigated the effect of β-endorphin on the activities of mitogen-activated protein kinases in cultured human articular chondrocytes in order to elucidate its effect on cartilage. Monolayer cultures of chondrocytes obtained from patients undergoing total knee arthroplasty were treated with 60, 600, or 6000 ng/ml β-endorphin, or 100 ng/ml naltrexone combined with 600 ng/ml β-endorphin. The regulation of three major mitogen-activated protein kinases phosphorylation, ERKp44/p42, p38, and JNK, was determined by Western blotting. We also examined the influence of specific mitogen-activated protein kinase inhibitors on IL-1β protein levels during β-endorphin stimulation. The results demonstrate that β-endorphin, dependent on concentration and duration of stimulation, significantly affected the activation of the three mitogen-activated protein kinases in cultured human articular chondrocytes. Naltrexone in some cases significantly regulated the mitogen-activated protein kinases in different ways when added to β-endorphin 600 ng/ml. Furthermore, specific mitogen-activated protein kinase inhibitors hindered the increase of IL-1β during β-endorphin incubation. The effect of β-endorphin seen in this study is considered critical for the production of several mediators of cartilage damage in an arthritic joint.

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Section: Introductionmentioning

confidence: 99%

β-Endorphin Regulation of MAPKs in Cultured Human Articular Chondrocytes: MAPK Inhibitors Prevent the Increase of IL-1β Protein Levels During β-Endorphin Stimulation

Andjelkov¹,

Elvenes²,

Knutsen³

et al. 2007

Cell Communication & Adhesion

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“…They were found to induce fibroblast proliferation, growth of capillaries, and enhance both the maturation of granulation tissue and the epithelization of the defect. 6 The detection of functional m-opioid receptors on human chondrocyte membranes 7 could suggest that m-opioid receptor agonists might influence human cartilage under both normal and pathological conditions. Recent findings show that certain opioid analgesics significantly inhibit proliferation of primary human chondrocytes.…”

Section: Introductionmentioning

confidence: 99%

Detection of mRNA transcripts of truncated opiate precursor (POMC) in human cartilage

Andjelkov

Elvenes

Figenschau

et al. 2006

Cell Biochem. Funct.

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In the present study, we have investigated the presence of pro-opiomelanocortin C-terminal fragment derived-peptides in human articular cartilage and cultured chondrocytes. beta-Lipotropin and beta-endorphin were monitored in different cell cultures and biopsies using different techniques. Biopsies were taken from patients undergoing total knee arthroplasty due to osteoarthritis. Both fresh tissue sections and chondrocytes cultured in monolayer were used in the study. Immunohistochemistry, immunocytochemistry, reverse transcriptase-polymerase chain reaction and qualitative Western blots were carried out. The results of the reverse transcriptase-polymerase chain reaction showed transcription of a truncated-form of mRNA for pro-opiomelanocortin in native cartilage and cultured chondrocytes. There was no detection of endogenous production of beta-lipotropin or beta-endorphin in human articular chondrocytes, either in situ or in vitro. Whether pro-opiomelanocortin-derived peptides of non-cartilaginous origin are present in articular cartilage itself still remains unclear.

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“…5 As for the cellular occurrence of opioid receptors in the periphery, most interest has focused on immunocytes. 6 However, osteoblasts 7,8 and chondrocytes 9,10 have also been shown to be equipped with opioid receptors, although the functional significance of these findings are poorly understood. The corresponding endogenous ligands have also been reported to be produced by the cell types described.…”

Section: Introductionmentioning

confidence: 99%

Opioid peptides and receptors in joint tissues: Study in the rat

Bergström

Ahmed

et al. 2006

Journal Orthopaedic Research

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Using immunohistochemical and biochemical techniques, the occurrence of endogenous opioid peptides and their receptors in normal rat bone and joint tissues was investigated. Opioid receptors were detected, quantified, and characterized in homogenates from capsule/synovium and periosteum using radioligand binding assays. Receptor binding of the nonselective opioid [ 3 H]naloxone to tissue homogenates was stereospecific and saturable, showing similar characteristics to that of brain tissue, although with lower binding capacities. By immunohistochemistry, the neuronal occurrence of four different enkephalins was demonstrated in synovium, bone marrow, periosteum, and juxta-articular bone, whereas no neuronal dynorphin immunoreactivity was detected. Double-staining studies disclosed that enkephalins coexisted with substance P in primary afferent fibers. The applied techniques can be used to assess changes in the distribution of endogenous opioids and their receptors in joint tissues in conditions associated with pain and inflammation. The endogenous opioid system now demonstrated might be targeted and exploited therapeutically to obtain peripheral control of symptoms in joint disorders. ß

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Expression of functional μ-opioid receptors in human osteoarthritic cartilage and chondrocytes

Cited by 29 publications

References 22 publications

β-Endorphin Regulation of MAPKs in Cultured Human Articular Chondrocytes: MAPK Inhibitors Prevent the Increase of IL-1β Protein Levels During β-Endorphin Stimulation

β-Endorphin Regulation of MAPKs in Cultured Human Articular Chondrocytes: MAPK Inhibitors Prevent the Increase of IL-1β Protein Levels During β-Endorphin Stimulation

Detection of mRNA transcripts of truncated opiate precursor (POMC) in human cartilage

Opioid peptides and receptors in joint tissues: Study in the rat

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