Periodontal ligament stem cells in tissue remodeling: from mechanical forces to inflammatory signals

The periodontal ligament (PDL), a specialized fibrous connective tissue bridging cementum and alveolar bone, harbors periodontal ligament stem cells (PDLSCs) as its key regenerative cellular component. Within the oral cavity, PDLSCs are continually exposed to two predominant stimuli: mechanical forces and inflammatory signals. Under physiological conditions, PDLSCs experience cyclic loading forces during normal mastication. During orthodontic treatment, controlled mechanical force stimulates PDLSCs and mediates tooth movement. However, in pathological scenarios, pathological mechanical stress, whether from occlusal trauma or excessive orthodontic forces, can induce PDL damage, potentially leading to adverse outcomes such as root resorption or pathological alveolar bone loss. Additionally, bacterially-induced inflammation can trigger destructive PDL changes, including alveolar bone and soft tissue degradation. Crucially, PDLSCs serve as central regulators of both the pathogenesis and therapeutic resolution of these processes. This review comprehensively summarizes the modulatory roles of PDLSCs in alveolar bone remodeling under mechanical stimulation and inflammatory conditions. It covers the alterations in the biological properties and functions of PDLSCs, along with their interactions with other bone remodeling-related cells and the microenvironment. Moreover, this review emphasizes the mechanisms by which PDLSCs regulate alveolar bone remodeling.