Leptin attenuates hypoxia‐induced apoptosis in human periodontal ligament cells via the reactive oxygen species–hypoxia‐inducible factor‐1α pathway

Abstract

Hypoxia-induced apoptosis of human periodontal ligament cells (hPDLCs) is an important contributor to the progression of various periodontal diseases. Although leptin has been shown to protect connective tissue cells against hypoxia-induced injury, whether it might do so by attenuating hypoxia-induced apoptosis in hPDLCs remains unclear. Here, using CoCl 2 treatment, we simulated hypoxic conditions in hPDLCs and explored whether apoptosis and reactive oxygen species (ROS) levels were related to hypoxia. After small interfering RNA (siRNA) inhibition of leptin and hypoxia-inducible factor-1α (HIF-1α), the levels of apoptosis, ROS and leptin expression were measured.We showed that in CoCl 2 -treated hPDLCs, significantly higher cell apoptosis rates and ROS accumulation were observed. Cobalt chloride also increased leptin and HIF-1α expression in hPDLCs. Further investigation of the pathway demonstrated that inhibition of ROS attenuated hypoxia-induced cell apoptosis and leptin expression, whereas siRNA inhibition of leptin aggravated hypoxia-induced cell apoptosis and ROS accumulation. Hypoxia induces cell apoptosis and leptin expression in hPDLCs through the induction of ROS and HIF-1α pathways, and leptin shows feedback inhibition on ROS-mediated apoptosis in hPDLCs. These findings suggest a new application of leptin for hypoxic damage in periodontal diseases.

CoCl2‐Induced hypoxia promotes hPDLSCs osteogenic differentiation through AKT/mTOR/4EBP‐1/HIF‐1α signaling and facilitates the repair of alveolar bone defects

“…These discrepancies might be attributed to the multiple functions of HIF-1α. High expression of HIF-1α under hypoxia in hPDLSCs causes ROS accumulation (Gao, Zhu, et al, 2021) and activates autophagy (Zheng, Zhu, et al, 2021) and the MAPK pathways (Zhou et al, 2021), thus initiating apoptosis and inflammation. In our study, we used stem cells and a shorter CoCl 2 treatment time.…”

Programmed cell death of periodontal ligament cells

“…Specifically, hypoxia can induce the accumulation of hypoxiainducible factor-1α (HIF-1α) and ROS in HPDLCs (Gao et al, 2021).…”

“…Hypoxia can induce the apoptosis of HPDLCs. Specifically, hypoxia can induce the accumulation of hypoxia‐inducible factor‐1α (HIF‐1α) and ROS in HPDLCs (Gao et al, 2021). The exposure of periodontal fibroblasts to hypoxic conditions can also significantly increase the expression of p38 mitogen‐activated protein kinase (p‐38 MAPK), IL‐1β, IL‐6, TNF‐α, and ROS, while decreasing the activity of superoxide dismutase (SOD) (Figure 3).…”