LepR⁺ skeletal stem/progenitor cells in craniofacial tissues

Leptin receptor (LepR)⁺ stromal cells are widely recognized as skeletal stem/progenitor cells (SSPCs) in the bone marrow that generate osteolineage cells, and contribute to skeletal homeostasis under steady-state conditions and tissue repair. By expressing representative niche factors, including stem cell factor and C-X-C motif chemokine ligand 12, LepR⁺ SSPCs function as key microenvironmental components of the hematopoietic stem cell (HSC) niche. Over the past decade, genetic cell-labeling studies have identified LepR⁺ SSPCs in craniofacial tissues, including in the periodontal ligament and alveolar bone marrow, where they differentiate into osteoblasts and cementoblasts.

Emerging evidence indicates that periodontal LepR ⁺ cells contribute to orthodontic remodeling, periodontal repair, and extraction socket healing. Independent SSPC populations may coexist with LepR⁺ SSPCs in oral tissues and contribute in parallel to tissue homeostasis. Periodontal LepR⁺ cells also express HSC niche-associated factors, suggesting their possible role in the regulation of local immune and hematopoietic environments. Because oral tissues are continuously exposed to mechanical forces and the oral microbiome, LepR⁺ SSPCs in the oral environment may function through unique regulatory mechanisms that influence skeletal homeostasis and hematopoiesis.

In this review, current knowledge regarding LepR⁺ SSPCs in periodontal tissues is summarized, and their emerging roles in skeletal maintenance, tissue repair, and hematopoietic regulation is discussed. Further elucidation of the regulatory mechanisms governing these cells will advance understanding of oral skeletal and hematopoietic biology, and may provide new insights into oral health and regenerative strategies.