Crohn’s disease (CD) is an intractable inflammatory bowel disease, and dysbiosis, disruption of the intestinal microbiota, is associated with CD pathophysiology. ER stress, disruption of ER homeostasis in Paneth cells of the small intestine, and α-defensin misfolding have been reported in CD patients. Because α-defensins regulate the composition of the intestinal microbiota, their misfolding may cause dysbiosis. However, whether ER stress, α-defensin misfolding, and dysbiosis contribute to the pathophysiology of CD remains unknown. Here, we show that abnormal Paneth cells with markers of ER stress appear in SAMP1/YitFc, a mouse model of CD, along with disease progression. Those mice secrete reduced-form α-defensins that lack disulfide bonds into the intestinal lumen, a condition not found in normal mice, and reduced-form α-defensins correlate with dysbiosis during disease progression. Moreover, administration of reduced-form α-defensins to wild-type mice induces the dysbiosis. These data provide novel insights into CD pathogenesis induced by dysbiosis resulting from Paneth cell α-defensin misfolding and they suggest further that Paneth cells may be potential therapeutic targets.

To evaluate the efficacy of our current prophylactic strategy by investigating the incidence of subsequent vertebral body fractures (SVBFs) following balloon kyphoplasty (BKP). Overview of Literature: Although extensive studies have investigated the risk factors for SVBFs after BKP, few have reported on postoperative therapies to prevent SVBFs and have evaluated their effectiveness. Methods: This study enrolled 273 patients who underwent an initial BKP. To treat osteoporosis, parathyroid hormone (PTH) administration was started 1-2 weeks before BKP and continued for at least 6 months postoperatively. Corsets were applied for 3 months after the procedure. Rehabilitative interventions, including hip range-of-motion training, muscle strengthening exercises, and motion/ posture instruction, were started from the preoperative assessment time point and resumed 3 hours postoperatively. Corsets were used in all patients. Therefore, no grouping based on corset use was performed. PTH was used in 180 patients, and they were divided into the following two groups: PTH user group and PTH nonuser group. Rehabilitative interventions were provided to all patients for a median duration of 17 days. Patients who underwent rehabilitative intervention for <17 and ≥17 days were included in the short-term and long-term intervention groups, respectively. The incidences of SVBFs for these four groups were compared. Results: SVBF occurred in 29 patients (10.6%). The SVBF incidence among patients who were prescribed all three prophylactic measures was 6.2%. The PTH user group had a significantly lower incidence of distant vertebral body fractures as compared to the PTH nonuser group. The long-term rehabilitation group had a significantly lower incidence of SVBFs and adjacent vertebral body fractures within 50 postoperative days than the short-term group. Conclusions: A 17-day or longer rehabilitative intervention may lower the risk of early adjacent vertebral body fractures, and the use of PTH may reduce the risk of distant vertebral body fractures.