The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) & Key Laboratory of Oral Biomedicine Ministry of Education, School & Hospital of Stomatology, Wuhan University, China.
The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) & Key Laboratory of Oral Biomedicine Ministry of Education, School & Hospital of Stomatology, Wuhan University, China;, Email:
Pharmazie. 2020 May 1;75(5):213-217. doi: 10.1691/ph.2020.0336.
Connective tissue growth factor (CTGF/CCN2) is a secreted protein modulating various biological processes, such as proliferation, differentiation, and survival. Tumor necrosis factor-α (TNF-α), known as a proinflammatory factor, negatively regulates osteoblast differentiation and survival. However, the potential mechanisms of CCN2 in TNF-α-induced osteoblast apoptosis are not fully understood. In the present study, we found that CCN2 was expressed in osteoblasts and downregulated after treatment with TNF-α. Overexpression of CCN2 attenuated TNF-α-induced osteoblast apoptosis. Autophagy, a pro-survival biological behavior, was triggered by TNF-α stimulation, and CCN2 overexpression enhanced this process. Inhibition of autophagy by chloroquine (CQ) affected the anti-apoptotic effect of CCN2. Moreover, the phosphorylation levels of Akt and Erk were upregulated in CCN2-over expressed cells, and LY294002 and U1026 (which inhibited the Akt and Erk signaling pathways, respectively) reversed the effect of CCN2 on autophagy and cell survival enhancement. Our data suggest that CCN2 might be a positive regulator of osteoblast survival in TNF-α stimulation by enhancing autophagy through the Akt and Erk signaling pathways.
结缔组织生长因子 (CTGF/CCN2) 是一种分泌蛋白，可调节多种生物学过程，如增殖、分化和存活。肿瘤坏死因子-α (TNF-α) 作为一种促炎因子，负向调节成骨细胞分化和存活。然而，CCN2 在 TNF-α 诱导的成骨细胞凋亡中的潜在机制尚不完全清楚。在本研究中，我们发现 CCN2 在成骨细胞中表达，并在 TNF-α 处理后下调。CCN2 的过表达减弱了 TNF-α 诱导的成骨细胞凋亡。自噬是一种促进生存的生物学行为，被 TNF-α 刺激触发，CCN2 的过表达增强了这一过程。氯喹 (CQ) 抑制自噬会影响 CCN2 的抗凋亡作用。此外，CCN2 过表达细胞中 Akt 和 Erk 的磷酸化水平上调，LY294002 和 U1026（分别抑制 Akt 和 Erk 信号通路）逆转了 CCN2 对自噬和细胞存活增强的作用。我们的数据表明，CCN2 可能通过激活 Akt 和 Erk 信号通路增强自噬来促进成骨细胞存活，从而成为 TNF-α 刺激下成骨细胞存活的正调节剂。
