Leukemia inhibitory factor (LIF), the most pleiotropic member of the interleukin-6 family of cytokines, utilizes a receptor composed of LIF receptor β and gp130 [2]. It activates multiple signaling pathways such as JAK/STAT3, MAPK, AKT, and mTOR [1]. LIF is of great biological importance, being involved in processes like blastocyst implantation, placental formation, nervous system development, and maintaining the self-renewal and totipotency of stem cells [2]. Genetic models, like knockout mice, are valuable tools for studying its functions.

Lif-knockout mice have provided insights into its role in various biological processes. In tooth development, Lif-deficiency leads to iron transportation dysfunction in ameloblasts, with reduced iron content in incisors, shorter ameloblast cell length, and decreased expression of iron-transporting proteins Tfrc and Slc40a1, modulated through the Stat3 signaling pathway [3]. In bone, Lif-deficient mice show reduced bone mass, altered systemic iron metabolism, and increased susceptibility of osteoblasts to ferroptosis, characterized by changes in iron distribution, hepcidin expression, and ferroptosis-related proteins [4]. In dental pulp inflammation, Lif-deficiency alleviates experimental pulpitis by reducing pro-inflammatory cytokines and macrophage infiltration, as LIF promotes macrophage inflammatory response through a STAT3/p65-dependent pathway [5].

In conclusion, LIF plays essential roles in multiple biological processes including tooth and bone development, and modulation of inflammation. The study of Lif-knockout mouse models has revealed its significant contributions to these areas, highlighting its potential as a target for therapies related to dental, bone, and inflammatory diseases.