HMBOX1 attenuates LPS‑induced periodontal ligament stem cell injury by inhibiting CXCL10 expression through the NF‑κB signaling pathway

Abstract

Homeobox containing 1 (HMBOX1) is a member of the homeobox transcription factor family that has been reported to serve an important role in numerous biological processes. The present study aimed to determine the role of HMBOX1 in the pathogenesis of periodontitis. Human periodontal ligament stem cells (hPDLSCs) were treated with liposaccharide (LPS) and transfected with a HMBOX1 overexpression (Ov-HMBOX1) plasmid or small interfering (si)-C-X-C motif chemokine ligand 10 (CXCL10) plasmids. The effects of Ov-HMBOX1 on cell proliferation, inflammation and apoptosis were subsequently investigated using Cell Counting Kit-8, ELISA for analysis of IL-6, TNF-α and IL-1β levels, TUNEL and western blotting assays for analysis of Bcl-2, Bax, cleaved caspase-3 and caspase-3 levels, respectively. Furthermore, the potential effects of HMBOX1 on the mRNA and protein levels of CXCL10 and the NF-κB signaling pathway were investigated by using reverse transcription-quantitative PCR and western blotting. Finally, the physiological processes of lipopolysaccharide (LPS)-induced hPDLSCs overexpressing HMBOX1 were assessed following treatment with phorbol 12-myristate 13-acetate (PMA), a NF-κB agonist. The results revealed that Ov-HMBOX1 transfection promoted proliferation whilst alleviating inflammation and apoptosis in LPS-induced hPDLSCs. Ov-HMBOX1 reduced the expression of CXCL10 by suppressing the NF-κB signaling pathway. PMA treatment inhibited the proliferation of LPS-induced hPDLSCs transfected with Ov-HMBOX1, which was reversed by transfection with si-CXCL10. In conclusion, results of the present study provided evidence that HMBOX1 can attenuate LPS-induced hPDLSC injury by downregulating CXCL10 expression via the NF-κB signaling pathway, which may provide a novel insight into the development of potentially novel treatment strategies for periodontitis.

Beneficial Effects of Essential Oils from the Mediterranean Diet on Gut Microbiota and Their Metabolites in Ischemic Heart Disease and Type-2 Diabetes Mellitus

“…In addition, we found increased levels of CXCL10 in all groups supplemented with L-carnitine when compared with the control group. CXCL10 is a pro-inflammatory chemokine that can be secreted by numerous cell types in response to an inflammatory process, regulating cell recruitment [ 70 ]. Its function can be regulated by cytokines, such as IFNγ and TNFα [ 71 , 72 , 73 ], and it has been proposed, together with CXCL9 and CXCL11, as a biomarker for heart failure and left ventricular dysfunction [ 74 , 75 ].…”

HMBOX1, a member of the homeobox family: current research progress

“…At present, HMBOX1 has been confirmed to inhibit inflammation by targeting NF-κB, MAPK, and other forms of inflammatory signaling. HMBOX1 mitigates lipopolysaccharide (LPS)-induced human periodontal ligament stem cell injury by reducing CXCL10 expression through impeding the activation of the NF-κB signaling pathway [ 32 ]. In an endothelial model of atherosclerosis, HMBOX1 expression inhibited the endothelial inflammatory response induced by MAPK, the NF-κB pathway, and ROS activation [ 33 ].…”