Influence of bone morphogenetic protein (BMP) signaling and masticatory load on morphological alterations of the mouse mandible during postnatal development

• Published in: Archives of oral biology 2025-01, Vol.169, p.106096, Article 106096
• Main Authors: Uptegrove, Amber, Chen, Coral, Sahagun-Bisson, Madison, Kulkarni, Anshul K., Louie, Ke’ale W., Ueharu, Hiroki, Mishina, Yuji, Omi-Sugihara, Maiko
• Format: Article
• Language: English
• Subjects: Animals; BMP; Bone Morphogenetic Protein Receptors, Type I - genetics; Bone Morphogenetic Proteins - metabolism; Chondrocytes - metabolism; Condyle; Mandible; Mastication; Mastication - physiology; Mechanical loading; Mice; Mice, Knockout; Osteoblasts - metabolism; Signal Transduction; Soft diet; X-Ray Microtomography
• ISSN: 0003-9969; 1879-1506; 1879-1506
• DOI: 10.1016/j.archoralbio.2024.106096

Bone homeostasis relies on several contributing factors, encompassing growth factors and mechanical stimuli. While bone morphogenetic protein (BMP) signaling is acknowledged for its essential role in skeletal development, its specific impact on mandibular morphogenesis remains unexplored. Here, we investigated the involvement of BMP signaling and mechanical loading through mastication in postnatal mandibular morphogenesis. We employed conditional deletion of Bmpr1a in osteoblasts and chondrocytes via Osterix-Cre. Cre activity was induced at birth for the 3-week group and at three weeks for the 9-week and 12-week groups, respectively. The conditional knockout (cKO) and control mice were given either a regular diet (hard diet, HD) or a powdered diet (soft diet, SD) from 3 weeks until sample collection, followed by micro-CT and histological analysis. The cKO mice exhibited shorter anterior lengths and a posteriorly inclined ramus across all age groups compared to the control mice. The cKO mice displayed an enlarged hypertrophic cartilage area along with fewer osteoclast numbers in the subchondral bone of the condyle compared to the control group at three weeks, followed by a reduction in the cartilage area in the posterior region at twelve weeks. Superimposed imaging and histomorphometrical analysis of the condyle revealed that BMP signaling primarily affects the posterior part of the condyle, while mastication affects the anterior part. Using 3D landmark-based geometric morphometrics and histological assessments of the mandible, we demonstrated that BMP signaling and mechanical loading reciprocally contribute to the morphological alterations of the mandible and condyle during postnatal development. •BMP signaling plays a role in mandibular morphogenesis during postnatal development.•Reduced masticatory load leads to morphological alterations in the mandibular condyle.•BMP signaling and masticatory load reciprocally regulate condylar cartilage formation.