Lu Yahui, Ruan Xiaolei, Xiao Gang, Dai Yueming, Li Gen, Cai Guanhui, Zheng Lihe, Guan Zhaolan, Sun Wen, Wang Hua
Department of Orthodontics, Affiliated Hospital of Stomatology, Nanjing Medical University, Nanjing, China.
State Key Laboratory Cultivation Base of Research, Prevention and Treatment for Oral Diseases, Nanjing, China.
J Clin Periodontol. 2025 Jan;52(1):171-185. doi: 10.1111/jcpe.14076. Epub 2024 Oct 14.
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.
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.
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.
Lockd boosts the proliferation of M-MSCs but inhibits their osteogenic differentiation by interacting with SUZ12, potentially inhibiting osteogenic capability in the inflammatory microenvironment.
研究长链非编码RNA Lockd在炎症微环境中对下颌间充质干细胞（M-MSC）增殖和成骨能力的作用，重点关注其与SUZ12的相互作用。
利用lncR Lockd敲低/过表达细胞模型和小鼠牙周炎模型，我们探究了Lockd在炎症微环境中对M-MSC增殖和成骨能力的影响。多个数据库的预测结果和一系列挽救实验揭示了Lockd/SUZ12信号轴在炎症微环境中对M-MSC的调控作用。
发现Lockd可刺激M-MSC增殖，但损害其成骨分化。体外研究表明，Lockd的激活会负面抑制成骨分化过程，并最终可能影响牙周炎中的骨形成。机制上，阐明了Lockd与多梳抑制复合物2（PRC2）的核心成分SUZ12相互作用，并可能影响PRC2复合物在成骨基因表达中的作用。
Lockd通过与SUZ12相互作用促进M-MSC的增殖，但抑制其成骨分化，可能在炎症微环境中抑制成骨能力。
