Morphological characteristics of interalveolar septum and mandible in BMAL1 gene knockout mice

Abstract

Purpose: Circadian rhythm is associated with the pathogenesis of systemic disease and bone mineral metabolism. This study aimed to radiographically evaluate morphological characteristics of the interalveolar septum in circadian rhythm deficient animals. Methods: Heads of 10 brain and muscle arnt-like protein-1 (BMAL1)knockout (KO) mice and 10 wild-type mice sacrificed at 36 weeks were imaged using micro-computed tomography. The mean depth from the cementoenamel junction to the alveolar ridge (virtual bone sounding: VBS) of the interalveolar septum between the first and second molars, and the bone mineral density (BMD) of the interalveolar septum and the mandibular inferior cortex region were calculated. Tooth diameter was also measured. Results: The VBS of the interalveolar septum in the BMAL1-KO mice was significantly deeper than that in wild-type mice. The BMD in the BMAL1-KO mice was significantly lower than in the wild-type mice in both regions. No significant difference was observed in tooth diameter between BMAL1-KO and wild-type mice. Conclusion:These results suggest that low BMD in the interalveolar septum accelerates bone resorption in the interalveolar septum in BMAL1-KO mice. Keywords; BMAL1, bone mineral density, circadian rhythm, periodontitis Micro-computed tomography (micro-CT)Micro-CT examination was performed using the R_mCT system (Rigaku, Tokyo, Japan) for all subjects. Imaging conditions were as follows: tube voltage 90 kV, tube current 200 μA, exposure time 2 m, voxel size 20 × 20 × 20 μm 3 , matrix size 480 × 480 × 480. The center of x, y and z axis of the FOV was set at the center of the mandible at molar region,

Circadian clock—A promising scientific target in oral science

“…The molecular nature of circadian rhythm regulation and maintenance is a circadian clock genedependent transcription-translation feedback loop (Gold and Kinrys, 2019). Compared to WT mice, the structurally unstable PDLs showed rapid periodontal destruction in Bmal1 knockout mice; in addition, the bone of the interalveolar septum was obviously deeper, and the bone mineral density was significantly lower (Koshi et al, 2020;Maria and Witt-Enderby, 2014). Circadian clock disruption could enhance SIRT1/NAD + dissociation, which promotes NF-κB transcriptional activity, and the active NF-κB pathway promotes cytokine expression during the inflammatory processes of gingivitis and periodontitis (Nakahata et al, 2009).…”

Orthodontic Force–Induced BMAL1 in PDLCs Is a Vital Osteoclastic Activator

“…Indeed, global Bmal1 −/− mice showed a decreased bone mass in the interalveolar septum (Koshi et al 2020), mandible (Zhou et al 2018), and condyle cartilage (Yu et al 2020). Of note, conditional depletion of Bmal1 in Osx + -derived cells resulted in a distinctive low-bone mass phenotype caused by a concomitant increase in bone formation and bone resorption (Takarada et al 2017).…”

PER2 regulates odontoblastic differentiation of dental papilla cells in vitro via intracellular ATP content and reactive oxygen species levels

“…Major clock genes, Bmal1 and Per2 , were oscillating in a regular 24-hour circadian rhythm in tooth-derived stem cells, suggesting that Bmal1 and Per2 may be regulators of tooth development ( Furukawa et al, 2005 ; Hilbert et al, 2019 ; Jiang et al, 2022 ; Lacruz et al, 2012 ; Zheng et al, 2013 ). The role of Bmal1 in promoting oral and maxillofacial development has been previously investigated ( Hirai et al, 2018 ; Koshi et al, 2020 ; Liu et al, 2022 ; Zhao et al, 2018 ). In particular, Bmal1 was recently found to regulate dental pulp cell differentiation and dentin formation ( Xu et al, 2022 ).…”