Department of Woman, Child and General and Specialist Surgery, University of Campania "Luigi Vanvitelli," Naples, Italy.
Department of Experimental Medicine, University of Campania "Luigi Vanvitelli," Naples, Italy.
Inflamm Bowel Dis. 2022 Aug 1;28(8):1244-1253. doi: 10.1093/ibd/izac073.
The reduction of bone mineral density and osteoporosis have high impacts on the health of patients with inflammatory bowel diseases (IBD). We have previously shown that a dysregulated iron metabolism occurs in IBD and leads to a decrease in circulating iron concentration and excessive intracellular sequestration of iron. Studies suggest that iron overload significantly affects the bone, accelerating osteoclast (OC) differentiation and activation, promoting bone resorption. Moreover, we demonstrated that iron overload causes OC overactivity. The cannabinoid receptor type 2 (CB2) and the transient receptor potential vanilloid type-1 (TRPV1) are potential therapeutic targets for bone diseases. The aim of this study was to evaluate the roles of CB2 and TRPV1 receptors and of iron in the development of osteoporosis in pediatric IBD.
We differentiated OCs from peripheral blood mononuclear cells of patients with IBD and healthy donors and evaluated CB2 and TRPV1 receptor expression; OC activity, and iron metabolism by Western blot, TRAP assays, bone resorption assays, and iron assays. Moreover, we analyzed the effects of the pharmacological modulation of CB2 and TRPV1 receptors on OC activity and on the iron metabolism.
We confirmed the well-known roles of CB2 and TRPV1 receptors in bone metabolism and suggested that their stimulation can reduce the OC overactivity induced by iron, providing new insights into the pathogenesis of pediatric IBD-related bone resorption.
Stimulation of CB2 and TRPV1 could reduce IBD-related osteoporosis due to their direct effects on OC activity and to modulating the iron metabolism.
骨密度降低和骨质疏松症对炎症性肠病（IBD）患者的健康有很大影响。我们之前已经表明，IBD 中存在铁代谢失调，导致循环铁浓度降低和铁的细胞内过度蓄积。研究表明，铁过载会显著影响骨骼，加速破骨细胞（OC）分化和激活，促进骨质吸收。此外，我们还证明了铁过载会导致 OC 过度活跃。大麻素受体 2（CB2）和瞬时受体电位香草醛型 1（TRPV1）是骨疾病的潜在治疗靶点。本研究旨在评估 CB2 和 TRPV1 受体以及铁在小儿 IBD 中骨质疏松症发展中的作用。
我们从 IBD 患者和健康供体的外周血单核细胞中分化 OC，并通过 Western blot、TRAP 测定、骨吸收测定和铁测定评估 CB2 和 TRPV1 受体表达、OC 活性和铁代谢。此外，我们分析了 CB2 和 TRPV1 受体的药理学调节对 OC 活性和铁代谢的影响。
我们证实了 CB2 和 TRPV1 受体在骨代谢中的已知作用，并提出其刺激可减少铁诱导的 OC 过度活跃，为小儿 IBD 相关骨吸收的发病机制提供了新的见解。
刺激 CB2 和 TRPV1 可能会减少 IBD 相关的骨质疏松症，因为它们直接作用于 OC 活性并调节铁代谢。
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