Intra-articular therapies for osteoarthritis

Yu, Shirley P.; Hunter, David J.

doi:10.1080/14656566.2016.1232396

Cited by 33 publications

(26 citation statements)

References 136 publications

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“…Disease progression is usually slow but can ultimately lead to joint failure with pain and disability [ 35 , 36 ]. Current therapies only relieve the symptoms, but cannot stop or reverse cartilage degeneration and destruction [ 37 , 38 ] . Previous studies showed that MSC exosomes, which contain miRNAs, mRNAs, and proteins, are likely to be important mediators in cell–cell communication to induce changes in cell functions and processes [ 39 , 40 ].…”

Section: Discussionmentioning

confidence: 99%

Exosomes derived from miR-92a-3p-overexpressing human mesenchymal stem cells enhance chondrogenesis and suppress cartilage degradation via targeting WNT5A

et al. 2018

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BackgroundWNT5A is known to be involved in the pathogenesis of osteoarthritis. This study investigated the molecular mechanism of exosomal miR-92a-3p and WNT5A in chondrogenesis and cartilage degeneration.MethodsExosomal miR-92a-3p expression was assessed in vitro in a human mesenchymal stem cell (MSC) model of chondrogenesis and in normal and OA primary human chondrocytes (PHCs). MSCs and PHCs were treated with exosomes derived from MSC-miR-92a-3p (MSC-miR-92a-3p-Exos) or its antisense inhibitor (MSC-anti-miR-92a-3p-Exos), respectively. Small interfering RNAs (siRNAs) and luciferase reporter assay were used to reveal the molecular role of exosomal miR-92a-3p and WNT5A in chondrogenesis. The protective effect of exosomes in vivo was measured using Safranin-O and Fast Green staining and immunohistochemical staining.ResultsExosomal miR-92a-3p expression was elevated in the MSC chondrogenic exosome, while it was significantly reduced in the OA chondrocyte-secreted exosome compared with normal cartilage. Treatment with MSC-miR-92a-3p-Exos promoted cartilage proliferation and matrix genes expression in MSCs and PHCs, respectively. In contrast, treatment with MSC-anti-miR-92a-3p-Exos repressed chondrogenic differentiation and reduced cartilage matrix synthesis by enhancing the expression of WNT5A. Luciferase reporter assay demonstrated that miR-92a-3p suppressed the activity of a reporter construct containing the 3’-UTR and inhibited WNT5A expression in both MSCs and PHCs. MSC-miR-92a-3p-Exos inhibit cartilage degradation in the OA mice model.ConclusionsOur results suggest that exosomal miR-92a-3p regulates cartilage development and homeostasis by directly targeting WNT5A. This indicates that exosomal miR-92a-3p may act as a Wnt inhibitor and exhibits potential as a disease-modifying osteoarthritis drug.Electronic supplementary materialThe online version of this article (10.1186/s13287-018-1004-0) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Exosomes derived from miR-92a-3p-overexpressing human mesenchymal stem cells enhance chondrogenesis and suppress cartilage degradation via targeting WNT5A

et al. 2018

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“…It is characterized by progressive articular cartilage destruction and synovitis 42 , 43 . Current therapies attempt to relieve the symptoms, but they cannot stop or reverse the ongoing cartilage degeneration 4 , 44 . The ideal treatment aiming for an optimal OA joint repair should promote regenerative properties of chondrocytes and fight destructive effects of inflammation.…”

Section: Discussionmentioning

confidence: 99%

Mesenchymal Stromal/stem Cell-derived Extracellular Vesicles Promote Human Cartilage Regeneration In Vitro

Vonk¹,

Dooremalen²,

Liv³

et al. 2018

Theranostics

287

211

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Osteoarthritis (OA) is a rheumatic disease leading to chronic pain and disability with no effective treatment available. Recently, allogeneic human mesenchymal stromal/stem cells (MSC) entered clinical trials as a novel therapy for OA. Increasing evidence suggests that therapeutic efficacy of MSC depends on paracrine signalling. Here we investigated the role of extracellular vesicles (EVs) secreted by human bone marrow derived MSC (BMMSC) in human OA cartilage repair.Methods: To test the effect of BMMSC-EVs on OA cartilage inflammation, TNF-alpha-stimulated OA chondrocyte monolayer cultures were treated with BMMSC-EVs and pro-inflammatory gene expression was measured by qRT-PCR after 48 h. To assess the impact of BMMSC-EVs on cartilage regeneration, BMMSC-EVs were added to the regeneration cultures of human OA chondrocytes, which were analyzed after 4 weeks for glycosaminoglycan content by 1,9-dimethylmethylene blue (DMMB) assay. Furthermore, paraffin sections of the regenerated tissue were stained for proteoglycans (safranin-O) and type II collagen (immunostaining).Results: We show that BMMSC-EVs inhibit the adverse effects of inflammatory mediators on cartilage homeostasis. When co-cultured with OA chondrocytes, BMMSC-EVs abrogated the TNF-alpha-mediated upregulation of COX2 and pro-inflammatory interleukins and inhibited TNF-alpha-induced collagenase activity. BMMSC-EVs also promoted cartilage regeneration in vitro. Addition of BMMSC-EVs to cultures of chondrocytes isolated from OA patients stimulated production of proteoglycans and type II collagen by these cells.Conclusion: Our data demonstrate that BMMSC-EVs can be important mediators of cartilage repair and hold great promise as a novel therapeutic for cartilage regeneration and osteoarthritis.

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“…Although it is generally accepted that IA corticosteroids have positive short-term effects on pain in knee OA and are widely used by clinicians, significant variation in the magnitude of the response has been reported. 57 Pain improvement using a visual analog scale on a 0 to 100 scale has demonstrated mean changes ranging from 16.2 to 35.7 mm reported in a recent systematic review. 58 Yu and Hunter (2016) also cited the pain experience by individuals with OA to involve a complicated biopsychosocial model that involves catabolic and inflammatory cytokines and sensitization of nociceptive pathways by the activation of primary efferent nerves in response to inflammation or tissue injury.…”

Section: Factors That Might Affect a Response To Intra-articular Cortmentioning

confidence: 98%

“…58 Yu and Hunter (2016) also cited the pain experience by individuals with OA to involve a complicated biopsychosocial model that involves catabolic and inflammatory cytokines and sensitization of nociceptive pathways by the activation of primary efferent nerves in response to inflammation or tissue injury. 57 The relationship of pain to structural damage is very complicated and the concepts of differences in central perception exacerbate this poor relationship (►Table 6).…”

Section: Factors That Might Affect a Response To Intra-articular Cortmentioning

confidence: 99%

Intra-articular Corticosteroids for Knee Pain—What Have We Learned from the Equine Athlete and Current Best Practice

McIlwraith

Lattermann

2018

J Knee Surg

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The use of intra-articular corticosteroids for traumatic arthritis and osteoarthritis (OA) is common in the horse. The beneficial and deleterious effects of the principal corticosteroids used betamethasone esters (Celestone [Soluspan], methylprednisolone acetate [Depo Medrol], and triamcinolone acetonide [TA] [Vetalog or Kenalog]) have been defined for the horse. While TA has both disease-modifying as well as symptom-modifying effects, methyl prednisolone acetate has deleterious effects on the articular cartilage. Studies in traumatically injured joints show the same rationale (suppression of deleterious mediators associated with inflammation) and positive results from the use of TA in both equine and human patients. Studies in the experimental equine OA model allow for more in-depth knowledge of disease-modifying effects. Recent insights allow us to understand posttraumatic OA as an early consequence of joint injury that may require a more aggressive and proactive treatment approach than commonly applied to date.

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Intra-articular therapies for osteoarthritis

Cited by 33 publications

References 136 publications

Exosomes derived from miR-92a-3p-overexpressing human mesenchymal stem cells enhance chondrogenesis and suppress cartilage degradation via targeting WNT5A

Exosomes derived from miR-92a-3p-overexpressing human mesenchymal stem cells enhance chondrogenesis and suppress cartilage degradation via targeting WNT5A

Mesenchymal Stromal/stem Cell-derived Extracellular Vesicles Promote Human Cartilage Regeneration In Vitro

Intra-articular Corticosteroids for Knee Pain—What Have We Learned from the Equine Athlete and Current Best Practice

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