Dexamethasone: chondroprotective corticosteroid or catabolic killer?

Black, Rebecca Mae; Grodzinsky, Alan J.

doi:10.22203/ecm.v038a17

Cited by 63 publications

(42 citation statements)

References 97 publications

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“…Low concentrations of Dex were able to protect cartilage explants from TNF- α and high dosage suppressed GAG content loss [ 29 ]. Black et al suggested in IL-1 α -stimulated bovine cartilage explants that Dex treatment largely inhibited transcriptions of IL-6, MMP-3, and MMP-13 [ 30 ]. Therefore, in the present study, we chose Dex as our positive medicine to dampen RA in vitro experimental setting.…”

Section: Discussionmentioning

confidence: 99%

CypB-CD147 Signaling Is Involved in Crosstalk between Cartilage and FLS in Collagen-Induced Arthritis

Wang

Fan

et al. 2020

Mediators of Inflammation

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To investigate the crosstalk between cartilage and fibroblast-like synoviocytes (FLS) in rheumatoid arthritis (RA), we adopted an in vitro coculture system model of collagen-induced arthritis (CIA) cartilage and CIA FLS monolayer. CIA rat samples of the synovium and femur head were collected for isolation of FLS and coculture system. Cartilages were treated with vehicle (Ctrl group), 10 ng/mL interleukin- (IL-) 1α (IL-1α group), and 10 ng/mL IL-1α plus 10 μM dexamethasone (Dex group) for 3 days before coculture with FLS for further 2 days. After the coculture, FLS were collected to determine the influences of articular cartilage on synoviocytes. Whether the CypB-CD147 signaling pathway is involved in the interactions between cartilage and FLS is assayed. Results showed that IL-1α-stimulated CIA cartilage promoted the proliferation and reduced the apoptosis of FLS. Increased inflammatory cytokines and decreased p57 expression were found in cocultured FLS stimulated by IL-1α-challenged CIA cartilage. Upregulation of NF-κB and I-κB kinase β (IKK-β) and downregulation of the inhibitor of NF-κBα (I-κBα) protein were observed in cocultured FLS. After coculture, significant increases in the expression of cyclophilin B (CypB) and CD147 were observed in CIA cartilage and FLS, respectively. Furthermore, results of immunofluorescence staining showed that the anti-CD147 antibody significantly suppressed p65 nuclear translocation in cocultured FLS stimulated by IL-1α-challenged CIA cartilage. In conclusion, inflammatory effects in the cartilage-FLS coculture system are associated with the CypB-CD147 mediating NF-κB pathway which may further enhance the inflammation in RA.

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Section: Discussionmentioning

confidence: 99%

CypB-CD147 Signaling Is Involved in Crosstalk between Cartilage and FLS in Collagen-Induced Arthritis

Wang

Fan

et al. 2020

Mediators of Inflammation

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“…According to data from other studies, degenerative changes in the cartilage of the knee joints of adult rats are accompanied by ultrastructural changes; that is, a decrease in the amount of rough endoplasmic reticulum and Golgi apparatus, an increase in glycogen content after 5 weeks of DXM administration [34], an increase in cell mortality rate, a decrease in the length of endoplasmic reticulum, a decrease in the number of Golgi apparatus, and a decrease in mitochondrial pool and size after 3 weeks of DXM administration [35]. Taken together, the results on the effects of DXM on the articular cartilage in healthy animals are controversial; DXM has been shown to affect cartilage and chondrocytes depending on the treatment duration [36].…”

Section: Discussionmentioning

confidence: 99%

“…One of the mechanisms of the corticosteroids' effects may be associated with changes in GAGs. The GAG content seems to be increased after DXM injection by reducing the activity of extracellular degradation enzymes [36]. However, according to another work, 9-week administration of other corticosteroid drug cortisone to adult rabbits led to a gradual decrease in the component of GAG-the hexosamine concentration content in articular cartilage [38] and a 55% decrease in GAG content in epiphyseal and articular cartilages of pony foals knee joint after 3 months of treatment [33].…”

Section: Discussionmentioning

confidence: 99%

Long-Term Exposure to Temozolomide Affects Locomotor Activity and Cartilage Structure of Elderly Experimental Rats

et al. 2020

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Chemotherapy with temozolomide (TMZ) is an essential part of anticancer therapy of various malignant tumours; however, its long-term effects on patients’ health and life quality need to be further investigated. Here, we studied the effects of TMZ and/or companion drug dexamethasone (DXM) on the locomotor activity and cartilage structure of elderly Wistar rats (n = 40). Long-term TMZ treatment selectively inhibited the horizontal, but not vertical locomotor activity of the rats (6.7-fold, p < 0.01) and resulted in delamination of the superficial epiphyseal cartilage of the femoral epiphysis of knee joints, a 2-fold decrease in mean thickness of epiphyseal cartilage (p < 0.001), and changes in the proliferative and maturation cartilage zones ratio. The simultaneous use of DXM attenuated TMZ-induced changes in cartilage thickness and integrity and compensated the decrease in horizontal locomotor activity of experimental animals. Nevertheless, combined TMZ/DXM treatment still significantly affected the structure of proximal tibial, but not distal femoral epiphysis of knee joints of the rats. These changes were accompanied by the increased content of total glycosaminoglycans (GAGs) and their partial re-localisation from chondrocytes into tissue matrix, as well as the decrease in sulfated GAGs content in both compartments. Taken together, the results demonstrate that long-term treatment with TMZ results in a significant decrease in locomotor activity of elderly Wistar rats and the reorganisation of their knee joint cartilage structure, while DXM treatment attenuates those effects. So, use of DXM or chondroprotective drugs might be beneficial to maintain quality of life for TMZ-treated cancer patients.

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“…Among them, dexamethasone is the drug with fewer adverse side effects and wider clinical application. Thus, dexamethasone has been considered the front line drug to inhibit OA-induced inflammation [ 9 ].…”

Section: Introductionmentioning

confidence: 99%

Hyaluronan-Loaded Liposomal Dexamethasone–Diclofenac Nanoparticles for Local Osteoarthritis Treatment

Chang

Chiang

Kuo

et al. 2021

IJMS

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Osteoarthritis (OA) remains one of the common degenerative joint diseases and a major cause of pain and disability in older adult individuals. Oral administration of non-steroidal anti-inflammatory drugs (NSAIDs) (such as diclofenac, DIC) or intra-articular injected gluco-corticosteroids (such as dexamethasone, DEX) were the conventional treatment strategies for OA to reduce joint pain. Current limitations for both drugs including severe adverse effects with risks of toxicity were noted. The aim of the present study was to generate a novel OA treatment formulation hyaluronic acid (HA)-Liposomal (Lipo)-DIC/DEX to combat joint pain. The formulation was prepared by constructing DIC with DEX-loaded nanostructured lipid carriers Lipo-DIC/DEX mixed with hyaluronic acid (HA) for prolonged OA application. The prepared Lipo-DIC/DEX nanoparticles revealed the size as 103.6 ± 0.3 nm on average, zeta potential as −22.3 ± 4.6 mV, the entrapment efficiency of 90.5 ± 5.6%, and the DIC and DEX content was 22.5 ± 4.1 and 2.5 ± 0.6%, respectively. Evidence indicated that HA-Lipo-DIC/DEX could reach the effective working concentration in 4 h and sustained the drug-releasing time for at least 168 h. No significant toxicities but increased cell numbers were observed when HA-Lipo-DIC/DEX co-cultured with articular chondrocytes cells. Using live-animal In vivo imaging system (IVIS), intra-articular injection of each HA-Lipo-DIC/DEX sufficed to reduce knee joint inflammation in OA mice over a time span of four weeks. Single-dose injection could reduce the inflammation volume down to 77.5 ± 5.1% from initial over that time span. Our results provided the novel drug-releasing formulation with safety and efficiency which could be a promising system for osteoarthritis pain control.

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Dexamethasone: chondroprotective corticosteroid or catabolic killer?

Cited by 63 publications

References 97 publications

CypB-CD147 Signaling Is Involved in Crosstalk between Cartilage and FLS in Collagen-Induced Arthritis

CypB-CD147 Signaling Is Involved in Crosstalk between Cartilage and FLS in Collagen-Induced Arthritis

Long-Term Exposure to Temozolomide Affects Locomotor Activity and Cartilage Structure of Elderly Experimental Rats

Hyaluronan-Loaded Liposomal Dexamethasone–Diclofenac Nanoparticles for Local Osteoarthritis Treatment

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