title: Procyanidins Mitigate Osteoarthritis Pathogenesis by, at Least in Part, Suppressing Vascular Endothelial Growth Factor Signaling.
abstract: 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.
authors.affiliation: Departments of Orthopedic Surgery, Albert Einstein College of Medicine, Bronx, NY 10461, USA. angela.wang@einstein.yu.edu.|Departments of Radiation Oncology, Albert Einstein College of Medicine, Bronx, NY 10461, USA. angela.wang@einstein.yu.edu.
authors.forename: Angela
authors.initials: A
authors.lastname: Wang
authors.affiliation: Departments of Orthopedic Surgery, Albert Einstein College of Medicine, Bronx, NY 10461, USA. daniel.leong@einstein.yu.edu.|Departments of Radiation Oncology, Albert Einstein College of Medicine, Bronx, NY 10461, USA. daniel.leong@einstein.yu.edu.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Leong
authors.affiliation: Departments of Orthopedic Surgery, Albert Einstein College of Medicine, Bronx, NY 10461, USA. zhiyong.he@einstein.yu.edu.|Departments of Radiation Oncology, Albert Einstein College of Medicine, Bronx, NY 10461, USA. zhiyong.he@einstein.yu.edu.
authors.forename: Zhiyong
authors.initials: Z
authors.lastname: He
authors.affiliation: Departments of Orthopedic Surgery, Albert Einstein College of Medicine, Bronx, NY 10461, USA. lin.xu@einstein.yu.edu.|Departments of Radiation Oncology, Albert Einstein College of Medicine, Bronx, NY 10461, USA. lin.xu@einstein.yu.edu.
authors.forename: Lin
authors.initials: L
authors.lastname: Xu
authors.affiliation: Departments of Orthopedic Surgery, Albert Einstein College of Medicine, Bronx, NY 10461, USA. lidi.liu@einstein.yu.edu.|Departments of Radiation Oncology, Albert Einstein College of Medicine, Bronx, NY 10461, USA. lidi.liu@einstein.yu.edu.
authors.forename: Lidi
authors.initials: L
authors.lastname: Liu
authors.affiliation: Departments of Orthopedic Surgery, Albert Einstein College of Medicine, Bronx, NY 10461, USA. sukim@montefiore.org.
authors.forename: Sun Jin
authors.initials: SJ
authors.lastname: Kim
authors.affiliation: Departments of Orthopedic Surgery, Albert Einstein College of Medicine, Bronx, NY 10461, USA. dhirsh@montefiore.org.
authors.forename: David M
authors.initials: DM
authors.lastname: Hirsh
authors.affiliation: Departments of Orthopedic Surgery, Albert Einstein College of Medicine, Bronx, NY 10461, USA. jhardin@montefiore.org.
authors.forename: John A
authors.initials: JA
authors.lastname: Hardin
authors.affiliation: Departments of Orthopedic Surgery, Albert Einstein College of Medicine, Bronx, NY 10461, USA. ncobelli@montefiore.org.
authors.forename: Neil J
authors.initials: NJ
authors.lastname: Cobelli
authors.affiliation: Departments of Orthopedic Surgery, Albert Einstein College of Medicine, Bronx, NY 10461, USA. herb.sun@einstein.yu.edu.|Departments of Radiation Oncology, Albert Einstein College of Medicine, Bronx, NY 10461, USA. herb.sun@einstein.yu.edu.
authors.forename: Hui B
authors.initials: HB
authors.lastname: Sun
mesh_terms: D000818:Animals; D044946:Biflavonoids / Q000494:pharmacology / Q000627:therapeutic use*; D002392:Catechin / Q000494:pharmacology / Q000627:therapeutic use*; D002478:Cells, Cultured; D019902:Chondrocytes / Q000187:drug effects / Q000378:metabolism; D024043:Collagen Type II / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008875:Middle Aged; D010003:Osteoarthritis / Q000188:drug therapy* / Q000378:metabolism*; D010024:Osteoporosis / Q000188:drug therapy; D044945:Proanthocyanidins / Q000494:pharmacology / Q000627:therapeutic use*; D015398:Signal Transduction / Q000187:drug effects; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
chemical_list: D044946:Biflavonoids; D024043:Collagen Type II; D044945:Proanthocyanidins; D042461:Vascular Endothelial Growth Factor A; C479580:procyanidin B2; C479581:procyanidin B3; C017674:procyanidin; D002392:Catechin
keywords: VEGF; chondroprotection; nutraceuticals; osteoarthritis; pine bark extract; post-traumatic osteoarthritis; procyanidins