In vivo Identification of Periodontal Progenitor Cells

Abstract

The periodontal ligament contains progenitor cells; however, their identity and differentiation potential in vivo remain poorly characterized. Previous results have suggested that periodontal tissue progenitors reside in perivascular areas. Therefore, we utilized a lineage-tracing approach to identify and track periodontal progenitor cells from the perivascular region in vivo. We used an alpha-smooth muscle actin (αSMA) promoter-driven and tamoxifen-inducible Cre system (αSMACreERT2) that, in combination with a reporter mouse line (Ai9), permanently labels a cell population, termed 'SMA9'. To trace the differentiation of SMA9-labeled cells into osteoblasts/cementoblasts, we utilized a Col2.3GFP transgene, while expression of Scleraxis-GFP was used to follow differentiation into periodontal ligament fibroblasts during normal tissue formation and remodeling following injury. In uninjured three-week-old SMA9 mice, tamoxifen labeled a small population of cells in the periodontal ligament that expanded over time, particularly in the apical region of the root. By 17 days and 7 weeks after labeling, some SMA9-labeled cells expressed markers indicating differentiation into mature lineages, including cementocytes. Following injury, SMA9 cells expanded, and differentiated into cementoblasts, osteoblasts, and periodontal ligament fibroblasts. SMA9-labeled cells represent a source of progenitors that can give rise to mature osteoblasts, cementoblasts, and fibroblasts within the periodontium.

Scleraxis and osterix antagonistically regulate tensile force-responsive remodeling of the periodontal ligament and alveolar bone

“…2C), suggesting that the PDL is distinct from ligament binding to adjacent bones in terms of its anti-angiogenic property. It has been suggested that progenitor cells expressing alpha-smooth muscle actin (αSMA) reside in the perivascular regions of the PDL and differentiate into osteoblasts, cementoblasts and fibroblasts (Roguljic et al, 2013;San Miguel et al, 2010). Consistent with previous findings, Scx + cells were not localized in close proximity to the perivascular regions (empty arrowheads in Fig.…”

“…Scx + /Sox9 + progenitors contribute to the establishment of the junction between cartilage and tendon/ligament (Blitz et al, 2013;Sugimoto et al, 2013a remodeling and maintaining the junction between the cementum of the tooth and the alveolar bone. As reported previously, αSMA + progenitor/stem cells in the perivascular regions of the PDL can differentiate into osteoblasts, cementoblasts and fibroblasts (Roguljic et al, 2013;San Miguel et al, 2010). However, expression of αSMA in the PDL did not overlap with Scx expression, suggesting that fibroblastic Scx + PDL cells respond to the mechanical stress to quickly participate in PDL remodeling.…”

The rational use of animal models in the evaluation of novel bone regenerative therapies

“…Although most studies were conducted with bone marrow derived mesenchymal progenitor cells (MPCs), other tissues have been described to contain osteoprogenitor cells with similar regenerative potential including adipose tissue, muscle, umbilical cord blood, periosteum, dental pulp and periodontal ligament [4,[39][40][41][42][43][44][45]. The multilineage differentiation ability, paracrine effects and immunomodulatory properties of MPCs make them an ideal for tissue engineering and regenerative purposes [5,7,[46][47][48].…”

Odontogenic Tumors, WHO 2005: Where Do We Go from Here?

“…Ossifying fibroma, cementifying fibroma, cemento-ossifying fibroma, ossifying odontogenic fibroma and periodontoma have all been suggested in the past. Despite the fact that all definitions of cementum include its anatomic association with tooth roots, we prefer cemento-ossifying fibroma as the best name for this entity, because it is a well understood term and because laboratory evidence indicates that periodontal ligament stem cells can produce bone or cementum [25] and that the periodontal ligament and inner lamina dura of the tooth socket probably arise from odontogenic ectomesenchyme. The term cemento-ossifying fibroma also emphasizes that this is exclusively a lesion of the tooth bearing areas of the jaws and avoids confusion with similar long bone tumor terminology.…”