Clinically, many nail disorders accompany bone deformities, but whether the two defects are causally related is under debate. To investigate the potential interactions between the two tissue types, we analyzed epithelial-specific β-catenin deficient mice, in which nail differentiation is abrogated. These mice showed regression of not only the nail plate but also of the underlying digit bone. Characterization of these bone defects revealed active bone resorption, which is suppressed by Wnt activation in osteoblast and osteoclast precursors. Furthermore, we found that Wntless (Wls) expression, essential for Wnt ligand secretion, was lacking in the β-catenin deficient nail epithelium and that genetic deletion of Wls in the nail epithelium led to the lack of Wnt activation in osteoblast and osteoclast precursors and subsequently led to defective regression of the underlying digit bone. Together, these data show epithelial Wnt ligands can ultimately regulate Wnt signaling in osteoblasts and osteoclast precursors, known to regulate bone homeostasis. These results reveal a critical role for the nail epithelium on the digit bone during homeostatic regeneration and show that Wnt/β-catenin signaling is critical for this interaction.
Using cannabis to reduce psychological and physical distress, referred to as self-medication, is a significant risk factor for cannabis use disorder. To better understand this high-risk behavior, a sample of 290 young adults (ages 18–25; 45.6% female) were recruited from two U.S. universities in January and February of 2020 to complete a survey about their cannabis use and self-medication. Results: seventy-six percent endorsed using cannabis to reduce problems such as anxiety, sleep, depression, pain, loneliness, social discomfort, and concentration. When predicting reasons for self-medication with cannabis, logistic regression models showed that lower CUDIT-R scores, experiencing withdrawal, living in a state where cannabis was illegal, and being female were all associated with higher rates of self-medication. Withdrawal symptoms were tested to predict self-medication with cannabis, and only insomnia and loss of appetite were significant predictors. To further explore why young adults self-medicate, each of the original predictors were regressed on seven specified reasons for self-medication. Young adults experiencing withdrawal were more likely to self-medicate for pain. Participants living where cannabis is legal were less likely to self-medicate for anxiety and depression. Living where cannabis is illegal also significantly predicted self-medicating for social discomfort—though the overall model predicting social discomfort was statistically non-significant. Finally, female participants were more likely to self-medicate for anxiety. These results suggest widespread self-medication among young adults with likely CUD and underscore the complexity of their cannabis use. The findings have implications for understanding why young adults use cannabis in relation to psychological and physical distress and for accurately treating young adults with cannabis use disorder.
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