Spatiotemporal distribution of α-smooth muscle actin-positive mesenchymal cells during tooth development and mechanical remodeling of the murine periodontal ligament

The periodontal ligament (PDL) contains heterogeneous mesenchymal stem/progenitor cells that contribute to periodontal homeostasis and regeneration. However, the developmental origin and behavior of α-smooth muscle actin (αSMA)-positive cells remain poorly understood. This study investigated the spatiotemporal distribution of αSMA-positive cells during tooth development and their response to altered mechanical loading following extraction of the opposing mandibular molars in mice. Before tooth eruption, αSMA-positive cells were widely distributed throughout the dental follicles but became progressively restricted to the apical PDL during root formation and eruption. In contrast, c-kit immunoreactivity gradually disappeared from the apical PDL, whereas Gli1/tdTomato-positive cells partially co-localized with αSMA-positive cells. Following extraction of the opposing molars, the αSMA-positive area and the number of PCNA-positive cells transiently increased, while endomucin-positive blood vessels became dilated in the apical PDL. These findings demonstrate that αSMA-positive cells undergo dynamic developmental redistribution and rapidly respond to altered mechanical loading. Furthermore, the partial co-localization of αSMA and Gli1 suggests that at least a subset of αSMA-positive cells may represent a resident mechanosensitive mesenchymal progenitor population involved in periodontal homeostasis and remodeling, providing new insight into the biological basis of periodontal remodeling during orthodontic tooth movement and periodontal regeneration.