Kim, N.-K. | Search bioRxiv

bioRxiv2019

Dynamic healing and remodeling of mandibular ramus in segmental mobility and cortical overlap after intraoral vertical osteotomy

The ramus immediately after intraoral vertical ramus osteotomy (IVRO) shows segmental mobility, cortical overlap, and projection, which yield smooth-surfaced continuity and stability after one year. This study aimed to elucidate the three-dimensional (3D) morphological changes driven by regional healing and remodeling 12 months postoperatively (Post) and their relationships with the immediate postoperative (Imm) segmental overlapping pattern. We performed a retrospective study of the morphological change of mandibular ramus in terms of time and amount of cortical overlap after IVRO. 3D computed tomography data of 108 hemi-mandibles were analyzed by independent superimposition of Imm proximal and distal segment to Post mandible. Analysis showed extensive regional bone resorption and apposition resulting in a relatively flat-surfaced and morphologically intact Post ramus. The middle ramal remodeling was significantly associated with Imm overlapping patterns and Post mandibular movement, new bony projections of various shapes being observed at the posterior border of the Post ramus. The ramus after IVRO underwent dynamic morphological changes during healing/remodeling which were partly associated with Imm overlap. Moreover, the Post functional and smooth-surfaced ramus seems to have been facilitated by the close surgical approximation of segments and the postoperative mandibular functional rehabilitation, even with segmental positional changes.

pathology↗

bioRxiv2017

Building a schizophrenia genetic network: Evidence that Transcription Factor 4 regulates schizophrenia risk genes.

The transcription factor 4 (TCF4) locus is a robust association finding with schizophrenia (SZ), but little is known about the genes regulated by the encoded transcription factor. Therefore, we conducted chromatin immunoprecipitation sequencing (ChIP-seq) of TCF4 in neural-derived (SH-SY5Y) cells to identify genome-wide TCF4 binding sites, followed by data integration with SZ association findings. We identified 11,322 TCF4 binding sites overlapping in two ChIP-seq experiments. These sites are significantly enriched for the TCF4 Ebox binding motif (>85% having [≥]1 Ebox) and implicate a gene set enriched for genes down-regulated in TCF4 siRNA knockdown experiments, indicating the validity of our findings. The TCF4 gene set was also enriched among 1) Gene Ontology categories such as axon/neuronal development, 2) genes preferentially expressed in brain, in particular pyramidal neurons of the somatosensory cortex, and 3) genes down-regulated in post-mortem brain tissue from SZ patients (OR=2.8, permutation p<4x10-5). Considering genomic alignments, TCF4 binding sites significantly overlapped those for neural DNA binding proteins such as FOXP2 and the SZ-associated EP300. TCF4 binding sites were modestly enriched among SZ risk loci from the Psychiatric Genomic Consortium (OR=1.56, p=0.03). In total, 130 TCF4 binding sites occurred in 39 of the 108 regions published in 2014. Thirteen genes within the 108 loci had both a TCF4 binding site {+/-}10kb and were differentially expressed in siRNA knockdown experiments of TCF4, suggesting direct TCF4 regulation. These findings confirm TCF4 as an important regulator of neural genes and point towards functional interactions with potential relevance for SZ.

genetics↗