Glucocorticoid signaling and osteoarthritis

Savvidou, Olga D.; Milonaki, Mandy; Goumenos, Stavros; Flevas, Dimitrios A; Papagelopoulos, Panayiotis J.; Moutsatsou, Paraskevi

doi:10.1016/j.mce.2018.11.001

Cited by 38 publications

(23 citation statements)

References 182 publications

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“…IA administration of GCs is acknowledged to be a relatively effective, safe, adjunct conservative management. IA administration of GCs is recommended in cases of moderate to severe OA when patients fail to respond to NSAIDS (54). The American guidelines for treating knee OA recommend IA GCs for short-term pain relief and IA GCs combined with oral medication for better outcomes (55).…”

Section: Discussionmentioning

confidence: 99%

Dexamethasone-loaded thermo-sensitive hydrogel attenuates osteoarthritis by protecting cartilage and providing effective pain relief

Wang¹,

Xu²,

Fan³

et al. 2021

Ann Transl Med

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Background: We utilized the destabilization of medial meniscus (DMM)-induced mice to illustrate the osteoarthritis (OA) suppressing and pain-relieving effects of a novel prolonged-release intra-articular (IA)dexamethasone-loaded thermo-sensitive hydrogel (DLTH).Methods: The effects of temperature and pH on DLTH formation and in vitro DLTH release profile were assessed. C57BL/6J mice were randomly divided into three groups: Ctrl group Model group and DLTH group. The DLTH group received joint injections of 10 μL DLTH (1 mg/kg) into the right knee once a week from week 2 to week 11. We performed micro-computed tomography (Micro-CT) and histological analyses of safranin O-fast green, hematoxylin and eosin, and tartrate-resistant acid phosphatase in knee joints. We also carried out immunohistochemical (IHC) staining for matrix metalloproteinase-9 (MMP-9), MMP-13, and a disintegrin and metalloproteinase with thrombospondin motifs-5 in cartilage and Ki-67 in synovia. Pain behavioral testing was carried out in all mice. The serum content of prostaglandin E2 (PGE2) and real-time polymerase chain reaction (PCR) of inflammatory cytokines and pain-related factors in dorsal root ganglia (DRGs) were evaluated. Results: It took 20 minutes to form DLTH at pH 7.0 and 37 ℃. The cumulative release profiles of dexamethasone (Dex) from DLTH at 37 ℃ revealed a rapid release in the first 24 h and a sustained slow release for 7 days. In vivo study illustrated that DLTH attenuated OA bone destruction and ameliorated synovitis and progression of OA in DMM-induced mice. The chondroprotective effects of DLTH were mediated by decreased expressions of MMP-9, MMP-13, and ADAMTS-5. The results showed that IA-DLTH exerted pain-relieving effects in OA mice. Upregulation of nociceptive response time (NRT) and downregulations of serum PGE2, inflammatory factors, and pain-related mediators in DRGs of mice in the DLTH group were recorded. Conclusions: Data presented in this study elucidated that DLTH exhibited a long and lasting Dex release and it is a potential sustainable drug delivery system (DDS) to treat OA locally. IA-DLTH injection exerted chondroprotective and pain-relieving effects in DMM-induced arthritis. The involvement of MMP-9, MMP-13, ADAMTS-5, and inflammatory and pain-related factors, may account for the suppression of OA progression and pain.

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Section: Discussionmentioning

confidence: 99%

Dexamethasone-loaded thermo-sensitive hydrogel attenuates osteoarthritis by protecting cartilage and providing effective pain relief

Wang¹,

Xu²,

Fan³

et al. 2021

Ann Transl Med

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“…Corticosteroids has been wildly used in the management of osteoarthritis, rheumatoid arthritis and some sports injuries for decades [32][33][34]. However, there has been more and more evidence showed that corticosteroids had a degenerative-effect on several collagen-producing tissues, such as bone, tendons [35,36].…”

Section: Discussionmentioning

confidence: 99%

Continuous infusion of dexamethasone aggravates the damage of cartilage via upregulating p-AKT and impairing articular autophagy in experimental OA model

chen

Zhang

et al. 2020

Preprint

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Objective To explore the effect of dexamethasone (Dex) infusion on articular cartilage and the underlying mechanisms in vitro and in vivo. Methods Destabilization of medial meniscus (DMM)-induced OA mouse model was used in this study. The mice with Dex treatment were sacrificed and then the knee joint samples were obtained for pathological analysis. Mouse primary chondrocytes were isolated and cultured in the presence or absence of Dex, which were used for calcification analysis and western blot assay. Results Dex accelerated the loss of articular cartilage matrix in mice, while it aggravated the damage of cartilage in DMM-induced OA model at the late stage. The calcium content in calcified cartilage layer in the joints from Dex treated OA mice was significantly higher than that from control mice. Dex treatment enhanced mineralization of articular cartilage matrix and leaded to massive apoptosis of chondrocytes in OA model. In addition, Dex caused autophagy of chondrocytes in the early stage, which was decreased at the late stage of Dex treatment. Moreover, we found that the effect of Dex on the mineralization of articular cartilage matrix in mice was related to AKT activation. Conclusions Continuous infusion of Dex can enhance the calcification of cartilage via AKT activation and increase chondrocyte apoptosis through inhibiting autophagy, which aggravates the damage of articular cartilage and accelerates the progression of OA in vivo.

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“…In the literature, the mechanisms are attributed to effects on stromal cells, by increasing the expression of ECM molecules and reduction of degradative proteases. This had been investigated in OA models, cartilage explant cultures and in cartilage cell lines [reviewed in (10, 126)] (Figure 3).…”

Section: Glucocorticoids (Gcs) In Osteoarthritismentioning

confidence: 99%

A Jack of All Trades: Impact of Glucocorticoids on Cellular Cross-Talk in Osteoimmunology

et al. 2019

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Glucocorticoids (GCs) are known to have a strong impact on the immune system, metabolism, and bone homeostasis. While these functions have been long investigated separately in immunology, metabolism, or bone biology, the understanding of how GCs regulate the cellular cross-talk between innate immune cells, mesenchymal cells, and other stromal cells has been garnering attention rather recently. Here we review the recent findings of GC action in osteoporosis, inflammatory bone diseases (rheumatoid and osteoarthritis), and bone regeneration during fracture healing. We focus on studies of pre-clinical animal models that enable dissecting the role of GC actions in innate immune cells, stromal cells, and bone cells using conditional and function-selective mutant mice of the GC receptor (GR), or mice with impaired GC signaling. Importantly, GCs do not only directly affect cellular functions, but also influence the cross-talk between mesenchymal and immune cells, contributing to both beneficial and adverse effects of GCs. Given the importance of endogenous GCs as stress hormones and the wide prescription of pharmaceutical GCs, an improved understanding of GC action is decisive for tackling inflammatory bone diseases, osteoporosis, and aging.

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Glucocorticoid signaling and osteoarthritis

Cited by 38 publications

References 182 publications

Dexamethasone-loaded thermo-sensitive hydrogel attenuates osteoarthritis by protecting cartilage and providing effective pain relief

Dexamethasone-loaded thermo-sensitive hydrogel attenuates osteoarthritis by protecting cartilage and providing effective pain relief

Continuous infusion of dexamethasone aggravates the damage of cartilage via upregulating p-AKT and impairing articular autophagy in experimental OA model

A Jack of All Trades: Impact of Glucocorticoids on Cellular Cross-Talk in Osteoimmunology

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