Bone microstructural characteristics or positional changes of condyle head affect short-term condyle head resorption after orthognathic surgery.

Condylar resorption occurs in some cases after orthognathic surgery, and the risk factors associated with postoperative condylar head resorption have been extensively described. Nevertheless, even in cases with a combination of risk factors, postoperative condylar resorption may not appear. This study analyzed the microstructure and three-dimensional positional change of the condylar bone via imaging in patients who have undergone bimaxillary orthognathic surgery to determine whether the microstructure or condylar position differs between patients with and without postoperative condylar resorption. Among asymptomatic patients who underwent bimaxillary surgery between April 2021 and March 2022 at our department, 17 patients were analyzed, limited to "female," "skeletal Class II," and "high-angle cases," which are known risk factors for mandibular head resorption. Multidetector computed tomography was performed on these patients before and 6 months after surgery, and the bone microstructure of the condylar head and the three-dimensional positional changes of the condylar bone and the proximal bony fragments were compared with the presence of postoperative condyle resorption using the bone morphology software TRI/3D-BON. Patients with condylar bone abnormalities before surgery and those with high trabecular bone density can develop postoperative resorption if the condyle is misaligned by surgery.

The scaffold protein JIP3 functions as a downstream effector of the small GTPase ARF6 to regulate neurite morphogenesis of cortical neurons.

The small GTPase ADP-ribosylation factor 6 (ARF6) plays crucial roles in a wide variety of cell functions. To better understand the molecular mechanisms of ARF6-mediated signaling and cellular functions, we sought new ARF6-binding proteins in the mouse brain. We identified the signaling scaffold protein JNK-interacting protein 3 (JIP3), which is exclusively expressed in neurons, as a downstream effector of ARF6. Overexpression of a unique dominant negative mutant of ARF6, which was unable to interact with JIP3, and knockdown of JIP3 in mouse cortical neurons stimulated the elongation and branching of neurites. These results provide evidence that ARF6/JIP3 signaling regulates neurite morphogenesis.

Phospholipase D2 functions as a downstream signaling molecule of MAP kinase pathway in L1-stimulated neurite outgrowth of cerebellar granule neurons.

Stimulation of the neuronal cell adhesion molecule L1 in cerebellar granule neurons (CGNs) enhances neurite outgrowth and this response is inhibited by the primary alcohol ethanol. Because primary alcohols suppress the formation of the signaling lipid phosphatidic acid (PA) by phospholipase D (PLD), this observation prompted us to investigate whether PLD plays a role in the L1-mediated neurite outgrowth in CGNs. In the cerebellum of postnatal day 8 mice, PLD2 protein was abundantly expressed, while PLD1 expression was not detected. The L1-stimulated neurite outgrowth was inhibited by primary alcohols and by overexpression of lipase-deficient PLD2. Increases in cellular PA levels by direct PA application or overexpression of wild-type PLD2 mimicked the L1-dependent stimulation of neurite outgrowth. Furthermore, it was found that L1 stimulation in CGNs increased PLD activity concomitantly with phosphorylation of extracellular signal-regulated kinase (ERK), both of which were inhibited by the MAP kinase-ERK kinase (MEK) inhibitor. These results provide evidence that PLD2 functions as a downstream signaling molecule of ERK to mediate the L1-dependent neurite outgrowth of CGNs, a mechanism that may be related to alcohol-related neurodevelopmental disorders.