0000000000023745
AUTHOR
Victoria Clérigues
The CO-releasing molecule CORM-2 is a novel regulator of the inflammatory process in osteoarthritic chondrocytes
Previous work has shown that the CO-releasing molecule CORM-2 protects against cartilage degradation. The aim of this study was to examine whether CORM-2 can control the production of inflammatory mediators in osteoarthritic chondrocytes and determine the mechanisms involved.Primary cultures of chondrocytes from OA patients were stimulated with IL-1beta. The production of reactive oxygen species, nitrite, PGE(2), TNF-alpha and IL-1 receptor antagonist (IL-1Ra) were measured in the presence or absence of CORM-2. The expression of nitric oxide synthase-2 (NOS-2), cyclo-oxygenase-2 (COX-2) and microsomal PG E synthase-1 (mPGES-1) was followed by western blot and real-time PCR. Activation of nu…
Antioxidant and Antiinflammatory Properties of Heme Oxygenase-1 in Osteoarthritic Articular Cells
Heme oxygenase-1 (HO-1) is induced in cells by various stimuli as a defense system against oxidative stress. It is known that reactive oxygen species (ROS) participates in the initiation and progression of osteoarthritis (OA) and several antioxidant systems may protect cartilage components. HO-1 induction or CO release from CORM-2 counteracts oxidative stress and protects against proinflammatory and catabolic effects of interleukin-1β in OA chondrocytes, osteoblasts, and synoviocytes as well as in OA osteochondral explants. Both approaches have been able to downregulate the production of mediators such as reactive oxygen species, nitric oxide, matrix metalloproteinases, prostaglandin E2, cy…
Heme oxygenase-1 mediates protective effects on inflammatory, catabolic and senescence responses induced by interleukin-1β in osteoarthritic osteoblasts
Osteoarthritis (OA) is a chronic degenerative joint disease showing altered bone metabolism. Osteoblasts contribute to the regulation of cartilage metabolism and bone remodeling. We have shown previously that induction of heme oxygenase-1 (HO-1) protects OA cartilage against inflammatory and degradative responses. In this study, we investigated the effects of HO-1 induction on OA osteoblast metabolism. HO-1 was induced with cobalt protoporphyrin IX (CoPP) and by transduction with LV-HO-1. In osteoblasts stimulated with interleukin (IL)-1β, CoPP enhanced mineralization, the expression of a number of markers of osteoblast differentiation such as Runx2, bone morphogenetic protein-2, osteocalci…
Haem oxygenase-1 counteracts the effects of interleukin-1β on inflammatory and senescence markers in cartilage-subchondral bone explants from osteoarthritic patients.
IL (interleukin)-1β plays an important role in cartilage extracellular matrix degradation and bone resorption in OA (osteoarthritis) through the induction of degradative enzymes and pro-inflammatory mediators. In the present study, we have determined the consequences of HO-1 (haem oxygenase-1) induction on markers of inflammation and senescence in the functional unit cartilage–subchondral bone stimulated with IL-1β. Cartilage–subchondral bone specimens were obtained from the knees of osteoarthritic patients. Treatment with the HO-1 inducer CoPP (cobalt protoporphyrin IX) counteracted the stimulatory effects of IL-1β on IL-6, nitrite, PGE2 (prostaglandin E2), TGF (transforming growth factor)…
Heme oxygenase-1 induction modulates microsomal prostaglandin E synthase-1 expression and prostaglandin E2 production in osteoarthritic chondrocytes
Pro-inflammatory cytokines such as interleukin-1beta (IL-1beta) may participate in the pathogenesis of cartilage damage in osteoarthritis (OA) through the production of catabolic enzymes and inflammatory mediators. Induction of heme oxygenase-1 (HO-1) has previously been shown to exert anti-inflammatory effects in different cell types. We have investigated whether HO-1 induction may modify chondrocyte viability and the production of relevant mediators such as oxidative stress and prostaglandin E(2) (PGE(2)) elicited by IL-1beta in OA chondrocytes. Chondrocytes were isolated from OA cartilage and used in primary culture. Cells were stimulated with IL-1beta in the absence or presence of the H…
Haem oxygenase-1 induction reverses the actions of interleukin-1β on hypoxia-inducible transcription factors and human chondrocyte metabolism in hypoxia
HO-1 (haem oxygenase-1) catalyses the degradation of haem and possesses anti-inflammatory and cytoprotective properties. The role of inflammatory mediators in the pathogenesis of OA (osteoarthritis) is becoming increasingly appreciated. In the present study, we investigated the effects of HO-1 induction in OA and healthy HACs (human articular chondrocytes) in response to inflammatory cytokine IL-1 β (interleukin-1β) under hypoxic conditions. Hypoxia was investigated as it is a more physiological condition of the avascular cartilage. Hypoxic signalling is mediated by HIFs (hypoxia-inducible factors), of which there are two main isoforms, HIF-1α and HIF-2α. Normal and OA chondrocytes were sti…
Influence of oxygen tension on the anti-inflammatory and chondroprotective effects of heme oxygenase-1 in healthy and osteoarthritic human chondrocytes
s / Osteoarthritis and Cartilage 20 (2012) S54–S296 S136 their isolation. The absence of cross-reaction with the IIA isoform was established by ELISA andWB. In addition, the Saos-2 cell linewas chosen to test a possible labelling of other fibrillar procollagens, mainly type I, V and XI. In fact, this cell line is described to synthesize the (a1)I, (a2)I, (a1)V, (a2)V, (a1)XI and (a2)XI, but no (a3)XI chains. No signal was detected on WB of cellular extracts or conditioned media with anti-pNIIB52, whereas antibodies to the collagen I, V and XI triple-helical parts revealed indeed the presence of proforms of these collagens. Conclusions: Anti-pNIIB52 antibodies allow a very sensitive and spec…
New molecular targets for the treatment of osteoarthritis.
Osteoarthritis (OA) is a chronic degenerative joint disorder characterized by destruction of the articular cartilage, subchondral bone alterations and synovitis. Current treatments are focused on symptomatic relief but they lack efficacy to control the progression of this disease which is a leading cause of disability. Therefore, the development of effective disease-modifying drugs is urgently needed. Different initiatives are in progress to define the molecular mechanisms involved in the initiation and progression of OA. These studies support the therapeutic potential of pathways relevant in joint metabolism such as Wnt/beta-catenin, discoidin domain receptor 2 or proteinase-activated rece…