Bone Morphogenetic Proteins in Periodontal Ligament Homeostasis

Objectives: Periodontal tissue is continually subject to environmental stimuli, such as inflammation and mechanical stress. The width of the periodontal ligament (PDL) is constant, and homeostasis is maintained. The periodontal ligament is not mineralized under physiological conditions, although it has similar characteristics to bone. However, the mechanisms regulating this are uncertain. This study showed the mechanism regulating mineralization of the periodontal ligament, by analyzing the expression of bone morphogenetic protein (BMP)-4 and the gene expression pattern of PDL cells.

Methods: The BMP-4 gene was transferred into periodontal ligament in vivo, and BMP expression and mineralization of the periodontal ligament were examined immunohistochemically and radiologically using soft x-rays. In addition, PDL cells established from temperature-sensitive SV40 large-T antigen transgenic rats, and fibroblasts from the skin and calvarial osteoblasts of neonatal Wistar rats were cultured in vitro. Mineralization was examined and expressions of osteoblast differentiation marker genes, matrix proteins, and transcription factors were analyzed using real-time PCR.

Results: It was confirmed that when the BMP-4 gene was introduced into muscle, bone formation resulted. Conversely, no bone formation was detected in the periodontal ligament, although BMP-4 protein was seen. Neither PDL cells nor skin fibroblasts showed mineralization, while osteoblasts made calcified nodules. Osteoblasts and PDL cells expressed alkaline phosphatase, osteopontin, osteocalcin, Runx2, and Osterix mRNA. PDL cells also expressed BMP-4 and BMP antagonists.

Conclusions: BMP-4 does not trigger bone formation in periodontal ligament, even if expressed excessively. PDL cells do not introduce mineralization under physiological conditions, although they have similar characteristics to osteoblasts. The results suggest that some periodontal ligament BMP antagonists prevent bone formation.