Impact of Myb deficiency on Rankl/Opg expression within the developing mouse mandible

The Rank-Rankl-Opg axis is a fundamental regulatory triad in bone development and remodelling. While extensively studied, novel modulators of this system continue to emerge, with the transcription factor Myb recently gaining attention due to its unexpected presence and physiological significance in tooth and bone, beyond its well-established role in haematopoiesis. To establish a baseline for normal development, we first elucidated the developmental dynamics of Rankl and Opg expression during prenatal mandibular development and osteocytogenesis in wild-type mice within distinct morphological regions of the developing mandible (incisor, diastema, molar), revealing intricate temporal expression patterns. Building upon this foundational understanding, we then investigated the hitherto uncharacterized impact of Myb deficiency on Rankl and Opg expression at their survival limit (prenatal day 15), using Myb knock-out mice. We observed a significant and region-specific upregulation of both Rankl and Opg expression in the molar region of Myb-deficient mandibles, as assessed by qPCR. Intriguingly, increased expression of both genes was also evident in the incisor region, while no significant changes were noted within the diastema. In contrast, Rank expression remained unaffected across all three segments. To confirm the reciprocal effect of Myb, we demonstrated that its overexpression in mandibular micromasses reciprocally altered Rankl and Opg expression. By confronting the established developmental dynamics with the effects of Myb deficiency and Myb's own expression pattern, we provide compelling evidence for a potent and direct influence of Myb on Rankl and Opg regulation, particularly prominent in the molar region. The observed temporal peaks of Myb and Rankl expression at the osteoblast-osteocyte transition further suggest broader, pivotal roles for Myb in osteogenesis. Our findings unravel Myb as a critical orchestrator of the Rank-Rankl-Opg system in craniofacial bone development, opening new avenues for understanding bone dysregulation.