Bevacizumab, an anti-vascular endothelial growth factor antibody, inhibits osteoarthritis

Nagai, Toshihiro; Sato, Masato; Kobayashi, M; Yokoyama, Munetaka; Tani, Yoshiki; Mochida, Joji

doi:10.1186/s13075-014-0427-y

Cited by 85 publications

(90 citation statements)

References 38 publications

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“…In cartilage, ADAMTS-4 levels did not change while MMP-13 was downregulated. These results are consistent with ACL-transection models in rabbits and rats [46] [47] [48], rodent meniscectomy [30, 49] models, and observations in canine cranial cruciate ligament tears [27]. Thus, non-cartilaginous soft tissues may be important sources of inflammatory molecules and proteases that contribute to cartilage matrix catabolism early after injury.…”

Section: Methodssupporting

confidence: 85%

Inflammation in joint injury and post-traumatic osteoarthritis

Lieberthal

Sambamurthy

Scanzello

2015

Osteoarthritis and Cartilage

356

330

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Inflammation is a variable feature of osteoarthritis (OA), associated with joint symptoms and progression of disease. Signs of inflammation can be observed in joint fluids and tissues from patients with joint injuries at risk for development of post-traumatic osteoarthritis (PTOA). Furthermore, inflammatory mechanisms are hypothesized to contribute to the risk of OA development and progression after injury. Animal models of PTOA have been instrumental in understanding factors and mechanisms involved in chronic progressive cartilage degradation observed after a predisposing injury. Specific aspects of inflammation observed in humans, including cytokine and chemokine production, synovial reaction, cellular infiltration and inflammatory pathway activation, are also observed in models of PTOA. Many of these models are now being utilized to understand the impact of post-injury inflammatory response on PTOA development and progression, including risk of progressive cartilage degeneration and development of chronic symptoms post-injury. As evidenced from these models, a vigorous inflammatory response occurs very early after joint injury but is then sustained at a lower level at the later phases. This early inflammatory response contributes to the development of PTOA features including cartilage erosion and is potentially modifiable, but specific mediators may also play a role in tissue repair. Although the optimal approach and timing of anti-inflammatory interventions after joint injury are yet to be determined, this body of work should provide hope for the future of disease modification tin PTOA.

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Section: Methodssupporting

confidence: 85%

Inflammation in joint injury and post-traumatic osteoarthritis

Lieberthal

Sambamurthy

Scanzello

2015

Osteoarthritis and Cartilage

356

330

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“…Injection of VEGF into animal joints induces OA and VEGF stimulates degeneration of articular chondrocytes 6 . Anti-VEGF therapy is therefore emerging as a potential OA treatment 7 .…”

Section: Introductionmentioning

confidence: 99%

Vascular Endothelial Growth Factor in Cartilage Development and Osteoarthritis

Nagao

Hamilton

et al. 2017

Sci Rep

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Genome wide studies indicate that vascular endothelial growth factor A (VEGF) is associated with osteoarthritis (OA), and increased VEGF expression correlates with increased disease severity. VEGF is also a chondrocyte survival factor during development and essential for bone formation, skeletal growth and postnatal homeostasis. This raises questions of how the important embryonic and postnatal functions of VEGF can be reconciled with an apparently destructive role in OA. Addressing these questions, we find that VEGF acts as a survival factor in growth plate chondrocytes during development but only up until a few weeks after birth in mice. It is also required for postnatal differentiation of articular chondrocytes and the timely ossification of bones in joint regions. In surgically induced knee OA in mice, a model of post-traumatic OA in humans, increased expression of VEGF is associated with catabolic processes in chondrocytes and synovial cells. Conditional knock-down of Vegf attenuates induced OA. Intra-articular anti-VEGF antibodies suppress OA progression, reduce levels of phosphorylated VEGFR2 in articular chondrocytes and synovial cells and reduce levels of phosphorylated VEGFR1 in dorsal root ganglia. Finally, oral administration of the VEGFR2 kinase inhibitor Vandetanib attenuates OA progression.

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“…The feasibility of treating OA by targeting VEGF has been previously demonstrated through the use of an anti-VEGF antibody in rabbits with OA [62]. However, adverse effects have been observed with anti-VEGF treatments, including vascular disturbances and regression of blood vessels [75], thus limiting their use chronically.…”

Section: Discussionmentioning

confidence: 99%

“…While the expression of VEGF is largely quiescent during maturity in adult non-OA cartilage, its expression is elevated in OA cartilage [56,57,58,59]. Furthermore, intra-articular injections of VEGF into the mouse knee joint [60] and the temporomandibular joint [61] induce OA, and intra-articular injections of VEGF-specific antibody bevacizumab mitigates OA progression in OA rabbits [62]. VEGF has also been demonstrated to regulate several pathways in OA pathogenesis, such as those involved in oxidative stress and catabolism [63].…”

Section: Introductionmentioning

confidence: 99%

Procyanidins Mitigate Osteoarthritis Pathogenesis by, at Least in Part, Suppressing Vascular Endothelial Growth Factor Signaling

Wang

Leong

et al. 2016

IJMS

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Procyanidins are a family of plant metabolites that have been suggested to mitigate osteoarthritis pathogenesis in mice. However, the underlying mechanism is largely unknown. This study aimed to determine whether procyanidins mitigate traumatic injury-induced osteoarthritis (OA) disease progression, and whether procyanidins exert a chondroprotective effect by, at least in part, suppressing vascular endothelial growth factor signaling. Procyanidins (extracts from pine bark), orally administered to mice subjected to surgery for destabilization of the medial meniscus, significantly slowed OA disease progression. Real-time polymerase chain reaction revealed that procyanidin treatment reduced expression of vascular endothelial growth factor and effectors in OA pathogenesis that are regulated by vascular endothelial growth factor. Procyanidin-suppressed vascular endothelial growth factor expression was correlated with reduced phosphorylation of vascular endothelial growth factor receptor 2 in human OA primary chondrocytes. Moreover, components of procyanidins, procyanidin B2 and procyanidin B3 exerted effects similar to those of total procyanidins in mitigating the OA-related gene expression profile in the primary culture of human OA chondrocytes in the presence of vascular endothelial growth factor. Together, these findings suggest procyanidins mitigate OA pathogenesis, which is mediated, at least in part, by suppressing vascular endothelial growth factor signaling.

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Bevacizumab, an anti-vascular endothelial growth factor antibody, inhibits osteoarthritis

Cited by 85 publications

References 38 publications

Inflammation in joint injury and post-traumatic osteoarthritis

Inflammation in joint injury and post-traumatic osteoarthritis

Vascular Endothelial Growth Factor in Cartilage Development and Osteoarthritis

Procyanidins Mitigate Osteoarthritis Pathogenesis by, at Least in Part, Suppressing Vascular Endothelial Growth Factor Signaling

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