Vascular Endothelial Growth Factor in Cartilage Development and Osteoarthritis.
Vascular Endothelial Growth Factor in Cartilage Development and Osteoarthritis.
复制标题
DOI：
10.1038/s41598-017-13417-w
复制
发表时间：
2017-10-12
影响因子：
4.6
通讯作者：
Olsen BR
中科院分区：
文献类型：
--
作者：
Nagao M;Hamilton JL;Kc R;Berendsen AD;Duan X;Cheong CW;Li X;Im HJ;Olsen BR
全基因组研究表明血管内皮生长因子A（VEGF）与骨关节炎（OA）相关，并且VEGF表达增加与疾病严重程度增加相关。VEGF也是发育期间的软骨细胞存活因子，并且对于骨形成、骨骼生长和出生后体内平衡是必需的。这就提出了一个问题，即VEGF在胚胎和出生后的重要功能如何与OA中明显的破坏性作用相协调。为了解决这些问题，我们发现VEGF在生长板软骨细胞的发育过程中作为一种生存因子，但仅在小鼠出生后几周内起作用。出生后关节软骨细胞的分化和关节区域骨骼的及时骨化也需要它。在手术诱导的小鼠膝关节OA（人类创伤后OA模型）中，VEGF表达增加与软骨细胞和滑膜细胞的分解代谢过程相关。VEGF的条件性敲低减弱诱导的OA。关节内抗VEGF抗体抑制OA进展，降低关节软骨细胞和滑膜细胞中磷酸化VEGFR2的水平，并降低背根神经节中磷酸化VEGFR1的水平。最后，口服VEGFR2激酶抑制剂Vandetanib可减缓OA进展。
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.
登录
查看更多内容
影响因子：
15.9
作者：
Hu, Kai;Olsen, Bjorn R.
通讯作者：
Olsen, Bjorn R.
影响因子：
4.6
作者：
Duan, Xuchen;Murata, Yurie;Berendsen, Agnes D.
通讯作者：
Berendsen, Agnes D.
影响因子：
7
作者：
Nagao M;Cheong CW;Olsen BR
通讯作者：
Olsen BR
影响因子：
15.9
作者：
Liu, Yanqiu;Berendsen, Agnes D.;Olsen, Bjorn R.
通讯作者：
Olsen, Bjorn R.
影响因子：
7
作者：
Gerwin, N.;Bendele, A. M.;Carlson, C. S.
通讯作者：
Carlson, C. S.