ABSTRACT
OBJECTIVE: Iron accumulation is associated with osteoporosis. This study aims to explore the effect of chronic iron accumulation induced by hepcidin1 deficiency on aging osteoporosis. METHODS: Iron accumulation in hepcidin1 knockout aging mice was assessed by atomic absorption spectroscopy and Perl's staining. Bone microarchitecture was observed using Micro-CT. Hepcidin, ferritin, oxidative stress, and markers of bone turnover in serum were detected by enzyme-linked immunosorbent assay. Bone formation and resorption markers were measured by real-time quantitative PCR. Cell aging was induced by D-galactose treatment. CCK-8, flow cytometry, EdU assays, and Alizarin red staining were performed to reveal the role of hepcidin1 knockout in cell model. Iron Colorimetric Assay Kit and western blot were applied to detect iron and ferritin levels in cells, respectively. RESULTS: In hepcidin1-knockout mice, the ferritin and iron contents in liver and tibia were significantly increased. Iron accumulation induced by hepcidin1 knockout caused a phenotype of low bone mass and deteriorated bone microarchitecture. Osteogenic marker was decreased and osteoclast marker was increased in mice, accompanied by increased oxidative stress level. The mRNA expression levels of osteoclast differentiation markers (RANKL, Mmp9, OPG, Trap, and CTSK) were up-regulated, while bone formation markers (OCN, ALP, Runx2, SP7, and Col-1) were down-regulated in model group, compared to wild type mice. In vitro, hepcidin1 knockdown inhibited proliferation and osteogenic differentiation, while promoted apoptosis, with increased levels of iron and ferritin. CONCLUSION: Iron accumulation induced by hepcidin1 deficiency aggravates the progression of aging osteoporosis via inhibiting osteogenesis and promoting osteoclast genesis.
Subject(s)
Osteogenesis , Osteoporosis , Mice , Animals , Osteoporosis/genetics , Osteoporosis/metabolism , Iron , Ferritins/pharmacology , Cell Differentiation/genetics , AgingABSTRACT
BACKGROUND: The occurrence of gastrointestinal stromal tumors (GISTs) in the small intestine is rare, and a case of wandering small intestinal stromal tumor has been rarely reported to date. Dissemination of this case can help inform future diagnosis and effective treatment. CASE SUMMARY: A 68-year-old patient presented to us with tarry stools. Computed tomography showed a mobile tumor moving widely within the abdominal cavity. As the laboratory data showed a low range of red blood cells and an immediate surgery was not indicated, we performed digital subtraction angiography and embolization to achieve hemostasis. Surgical resection was performed after the patient's condition improved. The tumor was successfully removed laparoscopically. Histological examination revealed submucosal GIST with infarction, which was of intermediate-risk, with mitotic count < 1 per 10 high-power field. Immunohistochemical studies revealed the following: CD117+, Dog1+, CD34+, SMA+, S100-, CK-, Des-, SOX-11-, STAT6-, Ki67 Hotspots 10%+. The patient was ultimately diagnosed with wandering small intestinal stromal tumor. CONCLUSION: When a highly vascularized tumor is clinically encountered in the small intestine, the possibility of stromal tumors should be considered. However, when the tumor cannot be visualized at its original location, the possibility of tumor migration is considered.
