BMPR1A in Periodontal Ligament Stem Cells Controls Periodontal Bone Homeostasis via Dual Roles

Periodontal homeostasis, the delicate balance between bone formation and resorption, is essential for tooth support. While Gli1 is an established marker for periodontal ligament stem cells (PDLSCs), the molecular pathways governing their homeostatic function remain largely unknown. We found that canonical bone morphogenetic protein (BMP) signaling activity is positively correlated with periodontal tissue status. To establish a causal relationship, we specifically ablated the BMP receptor type 1A ( Bmpr1a ) in Gli1 + PDLSCs of male mice. This genetic manipulation resulted in a periodontal destruction phenotype, featuring alveolar bone loss, cementum defects, and disrupted collagen fiber organization. At the mechanistic level, Bmpr1a deletion not only compromised the osteogenic capacity of Gli1 + PDLSCs but also promoted osteoclastogenesis. The enhanced bone resorption was associated with a close spatial proximity between Gli1-lineage cells and osteoclasts. Conditioned medium from BMPR1A -deficient human PDLSCs significantly enhanced osteoclast differentiation, and proteomic analysis identified an elevated RANKL/OPG ratio as the underlying cause. Our results uncover a novel role for PDLSCs in bone remodeling, demonstrating that BMPR1A in Gli1 + PDLSCs orchestrates periodontal homeostasis by coupling the direct promotion of osteogenic differentiation with the indirect inhibition of osteoclastogenesis via paracrine RANKL/OPG regulation.