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…

Control of Cell Migration and Inflammatory Mediators Production by CORM-2 in Osteoarthritic Synoviocytes

Background Osteoarthritis (OA) is the most widespread degenerative joint disease. Inflamed synovial cells contribute to the release of inflammatory and catabolic mediators during OA leading to destruction of articular tissues. We have shown previously that CO-releasing molecules exert anti-inflammatory effects in animal models and OA chondrocytes. We have studied the ability of CORM-2 to modify the migration of human OA synoviocytes and the production of chemokines and other mediators sustaining inflammatory and catabolic processes in the OA joint. Methodology/Principal Findings OA synoviocytes were stimulated with interleukin(IL)-1β in the absence or presence of CORM-2. Migration assay was…

Percutaneous osteoplasty in treatment of bone lymphangiomatosis

Primary bone lymphangiomatosis is a disease of unknown etiology that can cause lytic lesions in long bones, the pelvis, the spinal column and the cranium. We are presenting the case of a woman with localized bone lymphangiomatosis in the left knee. The authors believe this is the first case in which percutaneous osteoplasty was used in long bones for the treatment of bone lesions resulting from this disease showing good clinical results.

Mid- to Long-Term Outcome of Cementless Total Hip Arthroplasty in Younger Patients

Purpose. To assess mid- to long-term outcomes of cementless primary total hip arthroplasty (THA) in younger patients. Methods. Records of 28 women and 34 men (75 hips) aged 18 to 55 (mean, 38) years who underwent primary THA using a hydroxyapatite-coated stem and a threaded cup and had been followed up for a mean of 10 (6–15) years were reviewed. 13 of the patients had bilateral THAs. Clinical and radiographic outcomes were evaluated. Results. After a minimum follow-up of 7 (range, 7–14) years, 12 (16%) of the hips were revised, of which 8 (11%) were for the cup. The causes for revision were late deep infections (n=2), aseptic loosening of the cup (n=4), and polyethylene wear (n=6). No stem…

Expression of heme oxygenase-1 and regulation by cytokines in human osteoarthritic chondrocytes

Heme oxygenase-1 (HO-1) is implicated in the protection against tissue injury. We investigated the expression of this protein in cartilage sections and chondrocytes obtained from osteoarthritic patients. HO-1 was immunodetected in preparations from cartilage and also in chondrocytes cultured in the absence of stimulation. We found that HO-1 can be modulated by cytokines since the pro-inflammatory cytokines interleukin (IL)-1beta, IL-17 and tumour necrosis factor-alpha (TNF-alpha) down-regulated this protein, whereas the anti-inflammatory cytokine IL-10 exerted the opposite effect. Our results suggest a role for HO-1 as part of protective mechanisms against tissue injury in human cartilage.

AB0069 Conditioned media from adipose-derived mesenchymal stem cells decreases senescence and enhances collagen ii expression in osteoarthritic chondrocytes

Background Adipose-derived mesenchymal stem cells (ASC) might act as a cellular source of soluble factors exerting anti-inflammatory or trophic effects on cells. Osteoarthritis (OA) is characterized by the progressive loss of structure and functionality of articular cartilage. Objectives In the present study we explored the effect of conditioned medium from adipose-derived mesenchymal stem cells (ASC-CM) on the metabolism of OA chondrocytes in primary culture. Methods ADC were isolated from adipose tissue of patients subjected to abdominal lipectomy surgery, by collagenase treatment. Cells were incubated in DMEM/F12 + 15% human serum. Cell phenotype was analysed by flow cytometry with speci…

Paracrine effects of human adipose-derived mesenchymal stem cells in inflammatory stress-induced senescence features of osteoarthritic chondrocytes

Aging and exposure to stress would determine the chondrocyte phenotype in osteoarthritis (OA). In particular, chronic inflammation may contribute to stress-induced senescence of chondrocytes and cartilage degeneration during OA progression. Recent studies have shown that adipose-derived mesenchymal stem cells exert paracrine effects protecting against degenerative changes in chondrocytes. We have investigated whether the conditioned medium (CM) from adipose-derived mesenchymal stem cells may regulate senescence features induced by inflammatory stress in OA chondrocytes. Our results indicate that CM down-regulated senescence markers induced by interleukin-1β including senescence-associated β…

High mobility group box 1 potentiates the pro-inflammatory effects of interleukin-1β in osteoarthritic synoviocytes

Introduction High mobility group box 1 (HMGB1) is released by necrotic cells or secreted in response to inflammatory stimuli. Extracellular HMGB1 may act as a pro-inflammatory cytokine in rheumatoid arthritis. We have recently reported that HMGB1 is released by osteoarthritic synoviocytes after activation with interleukin-1beta (IL-1β) The present study investigated the role of HMGB1 in synovial inflammation in osteoarthritis (OA). Methods HMGB1 was determined in human synovium using immunohistochemistry, comparing normal to OA. OA synoviocytes were incubated with HMGB1 at 15 or 25 ng/ml in the absence or presence of IL-1β (10 ng/ml). Gene expression was analyzed by quantitative PCR and pro…

Haem oxygenase-1 down-regulates high mobility group box 1 and matrix metalloproteinases in osteoarthritic synoviocytes

Objectives. Activation of osteoarthritic synoviocytes by pro-inflammatory cytokines results in the release of biochemical mediators such as MMPs and high mobility group box 1 (HMGB1). Extracellular HMGB1 can play an important role in joint diseases as a mediator of synovitis. We have shown previously that haem oxygenase-1 (HO-1) exerts protective effects during inflammatory responses. In this study, we have examined whether HO-1 induction would be an effective strategy to control MMP and HMGB1 production in osteoarthritic synoviocytes. Methods. Osteoarthritic synoviocytes were obtained by digestion with collagenase and cultured until third passage. HO-1 was induced by cobalt protoporphyrin …

The Carbon Monoxide-Releasing Molecule Tricarbonyldichlororuthenium(II) Dimer Protects Human Osteoarthritic Chondrocytes and Cartilage from the Catabolic Actions of Interleukin-1β

We have investigated the effects of a carbon monoxide-releasing molecule, tricarbonyldichlororuthenium(II) dimer (CORM-2), on catabolic processes in human osteoarthritis (OA) cartilage and chondrocytes activated with interleukin-1beta. In these cells, proinflammatory cytokines induce the synthesis of matrix metalloproteinases (MMPs) and aggrecanases, including members of a disintegrin and metalloproteinase with thrombospondin domain (ADAMTS) family, which may contribute to cartilage loss. CORM-2 down-regulated MMP-1, MMP-3, MMP-10, MMP-13, and ADAMTS-5 in OA chondrocytes, and it inhibited cartilage degradation. These effects were accompanied by increased aggrecan synthesis and collagen II e…

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…

Conditioned Media from Adipose-Tissue-Derived Mesenchymal Stem Cells Downregulate Degradative Mediators Induced by Interleukin-1β in Osteoarthritic Chondrocytes

Osteoarthritis (OA) is the most frequent joint disorder and an important cause of disability. Recent studies have shown the potential of adipose-tissue-derived mesenchymal stem cells (AD-MSC) for cartilage repair. We have investigated whether conditioned medium from AD-MSC (CM) may regulate in OA chondrocytes a number of key mediators involved in cartilage degeneration. CM enhanced type II collagen expression in OA chondrocytes while decreasing matrix metalloproteinase (MMP) activity in cell supernatants as well as the levels of MMP-3 and MMP-13 proteins and mRNA in OA chondrocytes stimulated with interleukin- (IL-) 1β. In addition, CM increased IL-10 levels and counteracted the stimulating…

Conditioned media from adipose stem cells down-regulates senescence induced by interleukin-1β in osteoarthritic chondrocytes

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 regulates catabolic and anabolic processes in osteoarthritic chondrocytes

Pro-inflammatory cytokines, matrix metalloproteinases (MMPs) and other catabolic factors participate in the pathogenesis of cartilage damage in osteoarthritis (OA). Pro-inflammatory cytokines such as interleukin-1β (IL-1β) mediate cartilage degradation and might be involved in the progression of OA. Previously, we found that haem oxygenase-1 (HO-1) is down-regulated by pro-inflammatory cytokines and up-regulated by IL-10 in OA chondrocytes. The aim of this study was to determine whether HO-1 can modify the catabolic effects of IL-1β in OA cartilage and chondrocytes. Up-regulation of HO-1 by cobalt protoporphyrin IX significantly reduced glycosaminoglycan degradation elicited by IL-1β in OA …

A novel cyclo-oxygenase-2 inhibitor modulates catabolic and antiinflammatory mediators in osteoarthritis.

ITB (6-(p-bromophenyl)amino-7-(p-chlorophenyl)indazolo[2',3':1,5]-1,2,4-triazolo[4,3-a]-1,3,5-benzotriazepine) is a novel inhibitor of cyclo-oxygenase-2 (COX-2) with antiinflammatory activity in animal models. In the present study, we investigated the effect of this compound on the production of catabolic or antiinflammatory mediators in osteoarthritis (OA) cartilage. In OA cartilage explants, ITB inhibited the production of prostaglandin E(2) (PGE(2)), tumour necrosis factor-alpha (TNF-alpha) and matrix metalloproteinase-13 (MMP-13) in a concentration-dependent manner, whereas nitrite was partially reduced. On the contrary, ITB increased the production of interleukin (IL)-10 and the expres…

Anti-senescence and Anti-inflammatory Effects of the C-terminal Moiety of PTHrP Peptides in OA Osteoblasts.

Osteoarthritis (OA) is characterized by degenerative changes in the whole joint leading to physical disability in the elderly population. This condition is associated with altered bone metabolism in subchondral areas suggesting that therapeutic strategies aimed at modifying bone cell metabolism may be of interest. We have investigated the effects of several parathyroid hormone-related protein (PTHrP)-derived peptides (1-37): (N-terminal), (107-111) and (107-139) (C-terminal) on senescence features induced by inflammatory stress in human OA osteoblasts. Incubation of these primary cells with interleukin(IL)-1β led to an increased expression of senescence markers senescence-associated-β-galac…

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…

Post-synovectomy changes in the articular cartilage

Synovectomy of the left knee was performed in 37 immature rabbits, using the right knee for control. In the first set of experiments the articular cartilage was examined at weekly intervals for 8 weeks following the operation, paying particular attention to the metachromatic changes in the ground substance of the cartilage. In the second set of experiments, restoration of synovium was examined. In the third and fourth set of experiments, the uptake of S35 by the cartilage was assessed using autoradiography and densitometry. In the fifth set of experiments, alterations in S35 uptake by the chondrocitic cells of the cartilage were studied by electron microscopy.