Glucocorticoids (GC) are commonly used for the treatment of a wide variety of autoimmune, pulmonary, gastrointestinal, and malignancy conditions. One of the devastating side effects of GC use is osteoporotic fractures, particularly in the spine and hip. Bisphosphonates (BP) are the most commonly prescribed pharmacological agents for the prevention and treatment of GC‐induced osteoporosis (GIO). However, GIO is marked by reduced bone formation and BP serves mainly to decrease bone resorption. The WNT signaling pathway plays a major role in bone and mineral homeostasis. Previously, we demonstrated that overexpression of WNT16 in mice led to higher bone mineral density and improved bone microarchitecture and strength. We hypothesized that WNT16 overexpression would prevent bone loss due to glucocorticoid treatment in mice. To test our hypothesis, we treated adult wild‐type and WNT16‐transgenic mice with vehicle and GC (prednisolone; 2.1 mg/kg body weight) via slow‐release pellets for 28 days. We measured bone mass and microarchitecture by dual‐energy X‐ray absorptiometry (DXA) and micro‐CT, and performed gene expression and serum biochemical analysis. We found that GC treatment compared with the vehicle significantly decreased femoral areal bone mineral density (aBMD), bone mineral content (BMC), and cortical bone area and thickness in both wild‐type and transgenic female mice. In contrast, the trabecular bone parameters at distal femur were not significantly changed by GC treatment in male and female mice for both genotypes. Further, we observed significantly lower level of serum P1NP and a tendency of higher level of serum TRAP in wild‐type and transgenic mice due to GC treatment in both sexes. Gene expression analysis showed lower mRNA levels of Wnt16 , Opg , and Opg/Rankl ratio in GC‐treated female mice for both genotypes compared with the sex‐matched vehicle‐treated mice. These data suggest that although WNT16 overexpression resulted in higher baseline bone mineral density and bone volume per trabecular volume (BV/TV) in the transgenic mice, this was insufficient to prevent bone loss in mice due to glucocorticoid treatment. © 2018 The Authors JBMR Plus published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research.

Human papillomavirus type 16 (HPV 16) is the most common oncogenic type of HPV in cervical, anogenital, and head and neck cancers, making HPV 16 an important high-risk HPV (HR HPV) type. To create an environment permissible for viral maintenance and growth and to initiate and support oncogenesis, the HR HPV protein E6 functions to dysregulate normal cellular processes. HR HPV type 16 E6 (16E6) has previously been shown to bind cellular proteins in order to transcriptionally activate genes and to target regulatory proteins for degradation. We have identified an additional functional model for 16E6. First, 16E6 binds to cellular RNA processing and binding proteins, specifically cytoplasmic poly(A) binding proteins (PABPCs) and NFX1-123. Then, 16E6 hijacks those proteins’ functions to post-transcriptionally regulate cellular immortalization, growth, and differentiation genes and pathways in keratinocytes. In this review, we have highlighted studies that introduce this new model of 16E6 functionality. Understanding ways in which HR HPV dysregulates cellular processes—particularly at the level of post-transcriptional gene regulation—presents new ways to consider mechanisms underlying DNA tumor virus function and new areas for therapeutic target development in HPV-associated cancers.

In 2017, a total 1,708,569 chlamydial infections were reported to Centers for Disease Control and Prevention; the most prevalent sexually transmitted disease (STD). Chlamydia trachomatis primarily replicates in epithelial cells lining the reproductive tract. Epithelial cells recognize chlamydia through cell surface and cytosolic receptors, and/or endosomal innate receptors such as Toll‐like receptors (TLRs). The activation of these receptors triggers immune mechanisms that are required for chlamydial clearance. It was previously shown that Chlamydia muridarum (Cm) induces IFN‐β in oviduct epithelial cells in a TLR3‐dependent manner. TLR3's regulation of inflammatory chemicals involved in host defense against Cm infection led to the hypothesis that TLR3 plays a protective role against Cm‐induced genital tract pathology in congenic C57BL/6N mice. To test this hypothesis, wild‐type and TLR3‐deficient mice were treated with vehicle and Cm by swabbing the vaginal vault and cervix. Tissues were extracted from mice sacrificed on day 7, 21, or 42 post‐infection and fixed in 4% paraformaldehyde for 48 hrs. Paraffin‐embedded, 4‐μm sections containing cervix and both uterine horns and oviducts were stained with H&E. Genital tract sections (cervix, uterine body and horns, and oviducts) were microscopically examined and graded for the presence of acute inflammation (neutrophilic infiltrates), chronic inflammation (lymphocytic infiltrates), epithelial erosion and disruption, and luminal distension of uterine horns and oviducts using a semi qualitative pathology assessment. Inflammatory cell infiltrates, epithelial erosion and disruption were scored as follows: 0, normal; 1, mild; 2, moderate; 3, severe. All scoring was performed in a double‐blinded fashion with regards to the treatment groups. The results revealed an inflammatory immune response showing minute differences in both groups at day 7 (acute inflammation) in the oviducts, cervix and uterus. By day 21 (chronic inflammation), there was more inflammation seen in the WT group compared to the knock out TLR3 group. By day 42, there was mild chronic inflammation in the uterus in both groups; however, the knockout group had more cystic endometrial change in the uterus compared to the wild type group. In conclusion, the data suggest that TLR3 may promote the clearance of Cm.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.