Prospects for Therapies in Osteoarthritis

Ghouri, Asim; Conaghan, Philip G.

doi:10.1007/s00223-020-00672-9

Cited by 48 publications

(48 citation statements)

References 93 publications

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“…To date, pharmacological options used for OA management remain largely palliative [ 2 ] and innovative treatments are still at the research and development stage. Most of them comprise options with intra-articular delivery (i.e.,platelet rich plasma, PRP, fibroblast growth factors FGF, gene therapy, teriparatide, Wnt specific signal inhibitors) aimed to maximize efficacy and minimize systemic toxicity [ 35 , 36 ].…”

Section: Discussionmentioning

confidence: 99%

Boosting the Intra-Articular Efficacy of Low Dose Corticosteroid through a Biopolymeric Matrix: An In Vivo Model of Osteoarthritis

Tschon

Salamanna

Martini

et al. 2020

Cells

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The purpose of this study was to verify the efficacy of a single intra-articular (i.a.) injection of a hyaluronic acid-chitlac (HY-CTL) enriched with two low dosages of triamcinolone acetonide (TA, 2.0 mg/mL and 4.5 mg/mL), in comparison with HY-CTL alone, with a clinical control (TA 40 mg/mL) and with saline solution (NaCl) in an in vivo osteoarthritis (OA) model. Seven days after chemical induction of OA, 80 Sprague Dawley male rats were grouped into five arms (n = 16) and received a single i.a. injection of: 40 mg/mL TA, HY-CTL alone, HY-CTL with 2.0 mg/mL TA (RV2), HY-CTL with 4.5 mg/mL TA (RV4.5) and 0.9% NaCl. Pain sensitivity and Catwalk were performed at baseline and at 7, 14 and 21 days after the i.a. treatments. The histopathology of the joint, meniscus and synovial reaction, type II collagen expression and aggrecan expression were assessed 21 days after treatments. RV4.5 improved the local pain sensitivity in comparison with TA and NaCl. RV4.5 and TA exerted similar beneficial effects in all gait parameters. Histopathological analyses, measured by Osteoarthritis Research Society International (OARSI) and Kumar scores and by immunohistochemistry, evidenced that RV4.5 and TA reduced OA features in the same manner and showed a stronger type II collagen and aggrecan expression; both treatments reduced synovitis, as measured by Krenn score and, at the meniscus level, RV4.5 improved degenerative signs as evaluated by Pauli score. TA or RV4.5 treatments limited the local articular cartilage deterioration in knee OA with an improvement of the physical structure of articular cartilage, gait parameters, the sensitivity to local pain and a reduction of the synovial inflammation.

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Section: Discussionmentioning

confidence: 99%

Boosting the Intra-Articular Efficacy of Low Dose Corticosteroid through a Biopolymeric Matrix: An In Vivo Model of Osteoarthritis

Tschon

Salamanna

Martini

et al. 2020

Cells

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“…Osteoarthritis (OA) poses an enormous burden on the individual patient that adds up to a profound socioeconomic impact on health care sectors worldwide [ 1 ]. This justifies vigorous efforts to systematically study the molecular basis of disease onset and progression with the aim to develop innovative therapeutic strategies that interfere with the complex OA pathogenesis [ 2 , 3 ], currently culminating in multi-omics approaches to identify relevant molecular signatures [ 4 ]. Obviously, the strategic combination of work on clinical material with tailored in vitro models would be helpful to generate meaningful pathobiological results and improve translatability of new knowledge into clinical practice [ 5 ].…”

Section: Introductionmentioning

confidence: 99%

The Dysregulated Galectin Network Activates NF-κB to Induce Disease Markers and Matrix Degeneration in 3D Pellet Cultures of Osteoarthritic Chondrocytes

et al. 2020

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This work aimed to study the dysregulated network of galectins in OA chondrocyte pellets, and to assess whether their recently discovered activity as molecular switches of functional biomarkers results in degradation of extracellular matrix in vitro. Scaffold-free 3D pellet cultures were established of human OA chondrocytes. Expression and secretion of galectin(Gal)-1, -3, and -8 were monitored relative to 2D cultures or clinical tissue sections by RT-qPCR, immunohistochemistry and ELISAs. Exposure of 2D and 3D cultures to an in vivo-like galectin mixture (Gal-1 and Gal-8: 5 µg/ml, Gal-3: 1 µg/ml) was followed by the assessment of pellet size, immunohistochemical matrix staining, and/or quantification of MMP-1, -3, and -13. Application of inhibitors of NF-κB activation probed into the potential of intervening with galectin-induced matrix degradation. Galectin profiling revealed maintained dysregulation of Gal-1, -3, and -8 in pellet cultures, resembling the OA situation in situ. The presence of the galectin mixture promoted marked reduction of pellet size and loss of collagen type II-rich extracellular matrix, accompanied by the upregulation of MMP-1, -3, and -13. Inhibition of p65-phosphorylation by caffeic acid phenethyl ester effectively alleviated the detrimental effects of galectins, resulting in downregulated MMP secretion, reduced matrix breakdown and augmented pellet size. This study suggests that the dysregulated galectin network in OA cartilage leads to extracellular matrix breakdown, and provides encouraging evidence of the feasible inhibition of galectin-triggered activities. OA chondrocyte pellets have the potential to serve as in vitro disease model for further studies on galectins in OA onset and progression.

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“…Most trials conducted to date producing inconclusive results [26]. This means that the novel pharmacological agents, disease-modifying OA drugs (DMOADs) [27][28][29] and biological interventions that are currently being tested need to impact on joint structure (i.e. articular cartilage) and the symptoms of pain, even if they include surrogate endpoint and post-marketing confirmatory data under the accelerated drug approval regulations set forth by the Food and Drug Administration (FDA) [30].…”

Section: Existing Recommended Treatments For Oamentioning

confidence: 99%

Neuroscience and Neuroimmunology Solutions for Osteoarthritis Pain: Biological Drugs, Growth Factors, Peptides and Monoclonal Antibodies Targeting Peripheral Nerves

Mobasheri¹

2020

Preprint

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Neuroscience is a vast discipline that deals with the anatomy, biochemistry, molecular biology, physiology and pathophysiology of central and peripheral nerves. Advances made through basic, translational, and clinical research in the field of neuroscience have great potential for long-lasting and beneficial impacts on human health. The emerging field of biological therapy is intersecting with the disciplines of neuroscience and rheumatology, creating new horizons for interdisciplinary and applied research. Biological drugs, growth factors, neuropeptides and monoclonal antibodies are being developed and tested for the treatment of painful arthritic and rheumatic diseases. This concise communication focuses on the solutions provided by the fields of neuroscience and neuroimmunology for real-world clinical problems in the field of rheumatology, focusing on synovial joint pain and the emerging biological treatments that specifically target pathways implicated in osteoarthritis pain in peripheral nerves.

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Prospects for Therapies in Osteoarthritis

Cited by 48 publications

References 93 publications

Boosting the Intra-Articular Efficacy of Low Dose Corticosteroid through a Biopolymeric Matrix: An In Vivo Model of Osteoarthritis

Boosting the Intra-Articular Efficacy of Low Dose Corticosteroid through a Biopolymeric Matrix: An In Vivo Model of Osteoarthritis

The Dysregulated Galectin Network Activates NF-κB to Induce Disease Markers and Matrix Degeneration in 3D Pellet Cultures of Osteoarthritic Chondrocytes

Neuroscience and Neuroimmunology Solutions for Osteoarthritis Pain: Biological Drugs, Growth Factors, Peptides and Monoclonal Antibodies Targeting Peripheral Nerves

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