Suppression of NF-κB activation by curcumin leads to inhibition of expression of cyclo-oxygenase-2 and matrix metalloproteinase-9 in human articular chondrocytes: Implications for the treatment of osteoarthritis

Shakibaei, Mehdi; John, Thilo; Schulze‐Tanzil, Gundula; Lehmann, Irina; Mobasheri, Ali

doi:10.1016/j.bcp.2007.01.005

Cited by 315 publications

(268 citation statements)

References 47 publications

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“…These findings are consistent with those from studies of other cell types demonstrating the critical role of PI 3-kinase/Akt in the regulation of proinflammatory cytokines and the production of some MMPs (45)(46)(47)(48), as well as with other studies in which activation of the PI 3-kinase/Akt pathway was essential in up-regulating proinflammatory cytokine-induced and oncostatin M-induced MMP-9 and MMP-13 (46,48). In addition, activation of the PI 3-kinase/Akt pathway in osteoblasts has been demonstrated to play a crucial role in promoting the differentiation of these cells by preventing an apoptotic mechanism (47).…”

Section: Discussionsupporting

confidence: 91%

Activation of the receptor EphB4 by its specific ligand ephrin B2 in human osteoarthritic subchondral bone osteoblasts

Tat¹,

Pelletier²,

Amiable³

et al. 2008

Arthritis & Rheumatism

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Objective. Abnormal subchondral bone metabolism is involved in osteoarthritis (OA). It has been suggested that ephrin B2 and its specific receptor EphB4 participate in bone homeostasis. We previously reported that human OA subchondral bone osteoblasts could be classified into 2 subpopulations: low (L), having proresorption properties, and high (H), having proformation properties. The purpose of this study was to investigate the importance of the ephrin system in OA subchondral bone osteoblasts.Methods. The presence of the EphB4 receptor was determined by immunohistochemistry, and its expression level, modulation upon treatment, and consequences of activation by ephrin B2 were determined by quantitative polymerase chain reaction. The effects of ephrin B2 activation of the EphB4 receptor on bone resorption activity were also determined. EphB4 receptor activation signaling pathways were investigated by specific enzyme-linked immunosorbent assay.Results. EphB4 receptors were present in subchondral bone osteoblasts and osteocytes. Compared with normal and H-OA osteoblasts, EphB4 receptor expression levels were significantly increased in L-OA osteoblasts, with no difference between normal and H-OA osteoblasts. EphB4 receptor levels in L-OA osteoblasts were significantly up-regulated by prostaglandin E 2 (PGE 2 ) and interleukin-17 (IL-17). Ephrin B2, PGE 2 , and IL-17 significantly inhibited bone resorption activity in these cells. EphB4 activation by ephrin B2 significantly inhibited the expression of IL-1␤, IL-6, matrix metalloproteinase 1 (MMP-1), MMP-9, MMP-13, and RANKL, but not MMP-2 and osteoprotegerin. EphB4 receptor activation significantly inhibited the phosphatidylinositol 3-kinase/Akt pathway.Conclusion. This study is the first to provide evidence that EphB4 receptor activation by ephrin B2 in OA subchondral bone could affect abnormal metabolism in this tissue by inhibiting resorption factors and their activities. Ephrin B2 could be targeted as a specific therapeutic approach in the development of a diseasemodifying OA drug.Subchondral bone is made up of a specialized connective tissue formed by a mineralized matrix containing the specific type I collagen, proteoglycans, and several growth factors and cytokines, as well as bonespecific cell types (osteoblasts, osteocytes, and osteoclasts) (1,2). Osteoblast and osteoclast activities, either alone or in combination, contribute to the bone remodeling process, and any disturbance in the activities of these 2 cells is responsible for the development of altered bone metabolism.The ephrin B molecules (ephrin B1, ephrin B2, and ephrin B3) bind in a specific manner to their EphB

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Section: Discussionsupporting

confidence: 91%

Activation of the receptor EphB4 by its specific ligand ephrin B2 in human osteoarthritic subchondral bone osteoblasts

Tat¹,

Pelletier²,

Amiable³

et al. 2008

Arthritis & Rheumatism

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“…Thus, indirect MMP inhibition using nutraceuticals or plant-derived phytopharmaceuticals might provide a promising alternative to present therapeutic approaches. In this context, curcumin, resveratrol, or green tea catechins have already been investigated regarding their MMP-inhibitory actions (Shakibaei et al 2007;Lee and Moon 2005;Annabi et al 2007). …”

Section: Discussionmentioning

confidence: 99%

Caesalpinia sappan extract inhibits IL1β-mediated overexpression of matrix metalloproteinases in human chondrocytes

Toegel

Otero

et al. 2011

Genes Nutr

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Exacerbated production of matrix metalloproteinases (MMPs) is a key event in the progression of osteoarthritis (OA) and represents a promising target for the management of OA with nutraceuticals. In this study, we sought to determine the MMP-inhibitory activity of an ethanolic Caesalpinia sappan extract (CSE) in human OA chondrocytes. Thus, human articular chondrocytes isolated from OA cartilage and SW1353 chondrocytes were stimulated with Interleukin-1beta (IL1b), without or with pretreatment with CSE. Following viability assays, the production of MMP-2 and MMP-13 was assessed using ELISA, whereas mRNA levels of MMP-1, MMP-2, MMP-3, MMP-7, MMP-8, MMP-9, MMP-13 and TIMP-1, TIMP-2, TIMP-3 were quantified using RT-qPCR assays. Chondrocytes were co-transfected with a MMP-13 luciferase reporter construct and NF-kB p50 and p65 expression vectors in the presence or absence of CSE. In addition, the direct effect of CSE on the proteolytic activities of MMP-2 was evaluated using gelatin zymography. We found that CSE significantly suppressed IL1b-mediated upregulation of MMP-13 mRNA and protein levels via abrogation of the NF-kB(p65/p50)-driven MMP-13 promoter activation. We further observed that the levels of IL1b-induced MMP-1, MMP-3, MMP-7, and MMP-9 mRNA, but not TIMP mRNA levels, were down-regulated in chondrocytes in response to CSE. Zymographic results suggested that CSE did not directly interfere with the proteolytic activity of MMP-2. In summary, this study provides evidence for the MMP-inhibitory potential of CSE or CSE-derived compounds in human OA chondrocytes. The data indicate that the mechanism of this inhibition might, at least in part, involve targeting of NF-kB-mediated promoter activation.

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“…In human, inhibition of NF-kB activation could down-regulate pro-inflammatory cytokines IL-1b and TNF-a expression [68]. In addition, IkBa could inhibit NF-kB nuclear translocation in myogenic satellite cells [69].…”

Section: Optimal Dietary Protein Level Attenuated the Inflammatory Rementioning

confidence: 99%

Optimal dietary protein level improved growth, disease resistance, intestinal immune and physical barrier function of young grass carp (Ctenopharyngodon idella)

Jiang

et al. 2016

Fish & Shellfish Immunology

119

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Suppression of NF-κB activation by curcumin leads to inhibition of expression of cyclo-oxygenase-2 and matrix metalloproteinase-9 in human articular chondrocytes: Implications for the treatment of osteoarthritis

Cited by 315 publications

References 47 publications

Activation of the receptor EphB4 by its specific ligand ephrin B2 in human osteoarthritic subchondral bone osteoblasts

Activation of the receptor EphB4 by its specific ligand ephrin B2 in human osteoarthritic subchondral bone osteoblasts

Caesalpinia sappan extract inhibits IL1β-mediated overexpression of matrix metalloproteinases in human chondrocytes

Optimal dietary protein level improved growth, disease resistance, intestinal immune and physical barrier function of young grass carp (Ctenopharyngodon idella)

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