Distinct signaling pathways are involved in hypoxia- and IL-1-induced VEGF expression in human articular chondrocytes

作者：Murata M; Yudoh K; Nakamura H; Kato T; Inoue K; Chiba J; Nishioka K; Masuko Hongo K^*

来源：Journal of Orthopaedic Research, 2006, 24(7): 1544-1554.

DOI：10.1002/jor.20168

• vascular endothelial growth factor
• mitogen activated protein kinase
• hypoxia
• chondrocytes
• osteoarthritis

Recent data suggest that vascular endothelial growth factor (VEGF) is involved in the pathogenesis of osteoarthritis (OA). Cartilage is an avascular tissue, leading to a low cartilage 02 level. Thus, in a variety of pathologic or physiologic conditions, VEGF is partly regulated by hypoxic stress. The implications of hypoxia for VEGF expression by DA chondrocytes, however, are not known. We investigated the regulatory system of VEGF in CA chondrocytes under hypoxic conditions. Chondrocytes were obtained from articular cartilage of patients with OA. Cells were cultured and then incubated under hypoxic (95% N-2,5% CO2) or normoxic conditions, with or without interleukin IL-1 (10 ng/mL) stimulation. The mitogen activated protein kinase (MAPK) inhibitors were also used. VEGF levels in the culture supernatants were measured using an enzyme-linked immunosorbent assay. Western blot analysis was used to examine the expression of hypoxia inducible factor (HIF)-1 alpha. Hypoxia significantly increased VEGF levels (p < 0.05). Hypoxia-induced VEGF secretion was abolished by p38MAPK inhibitor, but not by JNK inhibitor. In contrast, IL-1induced VEGF secretion was blocked by JNK inhibitor, and not by p38MAPK inhibitor. Both hypoxia and IL-1-induced HIF-1 alpha were attenuated by p38 MAPK and JNK inhibitors. We demonstrate that hypoxia and IL-1 induce VEGF production in chondrocytes through distinct MAPK signaling pathways, indicating that VEGF is induced in a HIF-1-dependent or -independent manner in chondrocytes.

• 出版日期2006-7
• 单位河北医科大学