Lockd Enhances Mandibular Mesenchymal Stem Cell Proliferation While Inhibiting Osteogenic Capability via Binding With SUZ12 in the Inflammatory Microenvironment.

Abstract

AIM To investigate the role of lncRNA Lockd in mandibular mesenchymal stem cell (M-MSC) proliferation and osteogenic capability in the inflammatory microenvironment, focusing on its interaction with SUZ12. MATERIALS AND METHODS Using lncR Lockd knockdown/overexpression cell models and a murine periodontitis model, we explored Lockd's effects on M-MSC proliferation and osteogenic capability in the inflammatory microenvironment. Predictions from multiple databases and a series of rescue experiments revealed the regulatory role of the Lockd/SUZ12 signalling axis of M-MSC in the inflammatory microenvironment. RESULTS Lockd was found to stimulate M-MSC proliferation but impair osteogenic differentiation. The in vitro studies suggested that the activation of Lockd negatively inhibited the osteogenic differentiation process and may ultimately impact bone formation in periodontitis. Mechanistically, it was elucidated that Lockd interacts with SUZ12, a core component of the polycomb repressive complex 2 (PRC2), and may affect the PRC2 complex's role in osteogenic gene expression. CONCLUSIONS Lockd boosts the proliferation of M-MSCs but inhibits their osteogenic differentiation by interacting with SUZ12, potentially inhibiting osteogenic capability in the inflammatory microenvironment.