Transcriptome of the inner circular smooth muscle of the developing mouse intestine: Evidence for regulation of visceral smooth muscle genes by the hedgehog target gene, cJun.

BACKGROUND: Digestion is facilitated by coordinated contractions of the intestinal muscularis externa, a bilayered smooth muscle structure that is composed of inner circular muscles (ICM) and outer longitudinal muscles (OLM). We performed transcriptome analysis of intestinal mesenchyme tissue at E14.5, when the ICM, but not the OLM, is present, to investigate the transcriptional program of the ICM. RESULTS: We identified 3967 genes enriched in E14.5 intestinal mesenchyme. The gene expression profiles were clustered and annotated to known muscle genes, identifying a muscle-enriched subcluster. Using publically available in situ data, 127 genes were verified as expressed in ICM. Examination of the promoter and regulatory regions for these co-expressed genes revealed enrichment for cJUN transcription factor binding sites, and cJUN protein was enriched in ICM. cJUN ChIP-seq, performed at E14.5, revealed that cJUN regulatory regions contain characteristics of muscle enhancers. Finally, we show that cJun is a target of Hedgehog (Hh), a signaling pathway known to be important in smooth muscle development, and identify a cJun genomic enhancer that is responsive to Hh. CONCLUSIONS: This work provides the first transcriptional catalog for the developing ICM and suggests that cJun regulates gene expression in the ICM downstream of Hh signaling. Developmental Dynamics 245:614-626, 2016. © 2016 Wiley Periodicals, Inc.

Radiotherapy-Associated Pelvic Insufficiency Fracture Treated by Romosozumab: Course of CT Attenuations at L1 and L5.

Pelvic radiation therapy (RT) is a risk factor for pelvic insufficiency fracture, which may be accompanied by significant pain, decreased self-sufficiency, and impaired mobility. Assessment of bone density with "opportunistic" computed tomography (CT) attenuation of the L1 vertebral body can be used as a surrogate for dual-energy x-ray absorptiometry (DXA) scan and potentially be useful to follow bone changes in cancer patients who undergo surveillance CT imaging. The following is a case of a 60-year-old female who suffered a pelvic insufficiency fracture, after receiving chemotherapy and pelvic RT for endometrial cancer, for which she was treated with romosozumab, a sclerostin inhibitor used for postmenopausal women at high risk for insufficiency or fragility fracture. CT attenuation of the L1 and L5 vertebral bodies were measured prior to chemoradiation therapy, post-therapy, and before and after treatment with romosozumab. Pelvic RT was associated with declining CT attenuation, greater in magnitude at L5 vs L1 vertebral body, while treatment with romosozumab was associated with increase to baseline at L1, and improvement but not return to baseline at L5.