Long-term analgesic effect of a single dose of anti-NGF antibody on pain during motion without notable suppression of joint edema and lesion in a rat model of osteoarthritis

Ishikawa, Go; Koya, Yukari; Tanaka, Hiroaki; Nagakura, Yukinori

doi:10.1016/j.joca.2015.02.002

Cited by 46 publications

(47 citation statements)

References 29 publications

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“…Stabilization of the synovial compartment within OA joints is found to reduce posture imbalance and gait irregularity during movement 36, 37 . Plausible investigations were that miR-29aTg mice displayed slight responses to synovial thickening, inflammatory cell infiltration, and fibrosis.…”

Section: Discussionmentioning

confidence: 99%

MicroRNA-29a Counteracts Synovitis in Knee Osteoarthritis Pathogenesis by Targeting VEGF

Lee

Lian

et al. 2017

Sci Rep

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Synovitis contributes to the development of osteoarthritis (OA) of the knee. MicroRNAs regulate joint microenvironment homeostasis and deterioration. This study was undertaken to characterize the actions of microRNA-29a (miR-29a) to synovial remodeling in OA joints. Synovial specimens isolated from patients with end-stage OA knees showed abundant fibrotic matrix and vessel histopathology concomitant with weak miR-29a expression. In vitro, miR-29a knockdown caused synovial fibroblasts to exhibit high expressions of collagen III, TGF-β1, MMP9, MMP13, and ADAMTS5, whereas miR-29a overexpression diminished these joint-deleterious factors. In collagenase-mediated OA pathogenesis, miR-29a-overexpressing transgenic mice showed minor responses to hyperplasia, macrophage infiltration, fibrosis, hyperangiogenesis, and VEGF expression in synovial lesions. These effects mitigated articular cartilage loss and gait aberrance of injured joints. Intra-articular administration of miR-29a precursor lessened the collagenase aggravation of excessive synovial remodeling reactions and thereby sustained joint tissue integrity. miR-29a lowered VEGF production and angiogenic activities in synovial fibroblasts through targeting the 3′-UTR of VEGF. Taken together, miR-29a deficiency exacerbated synovitis pathogenesis in the end-stage OA knees. miR-29a signaling fends off excessive synovial angiogenesis and fibrosis, which delays joint destruction. This study sheds new light on the protective effects against synovial deterioration and the therapeutic advantage of miR-29a in OA knees.

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Section: Discussionmentioning

confidence: 99%

MicroRNA-29a Counteracts Synovitis in Knee Osteoarthritis Pathogenesis by Targeting VEGF

Lee

Lian

et al. 2017

Sci Rep

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“…In two rat OA models, meniscal transection and mono-iodoacetate (MIA)-induced OA, it was shown that pain responses to NGF locally administered into the knee cavity are increased in OA compared to non-OA joints [18], indicating that local production of NGF may be crucial for the generation of pain. In the rat MIA model, a single dose of anti-NGF antibody exerted a long-lasting beneficial effect on pain during motion, as assessed by monitoring gait [19]. A soluble NGF receptor fragment containing the NGF binding domain, TrkAd5, had a beneficial effect on weightbearing deficits 16 weeks after destabilization of the medial meniscus (DMM) in the mouse [20].…”

Section: Blockade Of Nerve Growth Factor Activitymentioning

confidence: 99%

Emerging Targets for the Management of Osteoarthritis Pain

Malfait

Miller

2016

Curr Osteoporos Rep

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Worldwide, osteoarthritis (OA) is one of the leading causes of chronic pain, for which adequate relief is not available. Ongoing peripheral input from the affected joint is a major factor in OA-associated pain. Therefore, this review focuses predominantly on peripheral targets emerging in the preclinical and clinical arena. Nerve growth factor is the most advanced of these targets, and its blockade has shown tremendous promise in clinical trials in knee OA. A number of different types of ion channels, including voltage-gated sodium channels and calcium channels, transient receptor potential channels and acid-sensing ion channels, are important for neuronal excitability and play a role in pain genesis. Few channel blockers have been tested in preclinical models of OA, with varying results. Finally, we discuss some examples of G-protein coupled receptors, which may offer attractive therapeutic strategies for OA pain, including receptors for bradykinin, calcitonin gene-related peptide, and chemokines. Since many of the pathways described above can be selectively and potently targeted, they offer an exciting opportunity for pain management in OA, either systemically or locally.

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“…Prophylactic treatment of rats with indomethacin prior to MIA injection was able to prevent TrkA upregulation in the DRG and reduce sensitivity to IA injection of NGF, but it had no effect on synovitis or joint swelling (50). In another study, a single systemic dose of an anti-NGF antibody 3 days after MIA injection resulted in decreased gait deficits by day 35, despite the fact that treatment did not affect joint swelling and development of macroscopic cartilage lesions (56). The relative contributions of the two different NGF receptors, TrkA and p75, have not been fully elucidated in the context of OA pain.…”

Section: Peripheral Sensitizationmentioning

confidence: 99%

The Role of Peripheral Nociceptive Neurons in the Pathophysiology of Osteoarthritis Pain

Miller

Tran

Obeidat

et al. 2015

Curr Osteoporos Rep

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Knee osteoarthritis is characterized by progressive damage and remodeling of all tissues in the knee joint. Pain is the main symptom associated with knee osteoarthritis. Recent clinical and pre-clinical studies shed light on the mechanisms that drive the pain associated with joint destruction. In this narrative review, we describe current knowledge regarding the changes in the peripheral and central nervous system that occur during the progression of osteoarthritis and discuss how therapeutic interventions may provide pain relief.

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Long-term analgesic effect of a single dose of anti-NGF antibody on pain during motion without notable suppression of joint edema and lesion in a rat model of osteoarthritis

Cited by 46 publications

References 29 publications

MicroRNA-29a Counteracts Synovitis in Knee Osteoarthritis Pathogenesis by Targeting VEGF

MicroRNA-29a Counteracts Synovitis in Knee Osteoarthritis Pathogenesis by Targeting VEGF

Emerging Targets for the Management of Osteoarthritis Pain

The Role of Peripheral Nociceptive Neurons in the Pathophysiology of Osteoarthritis Pain

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