Differential Iron Requirements for Osteoblast and Adipocyte Differentiation.
Differential Iron Requirements for Osteoblast and Adipocyte Differentiation.
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DOI：
10.1002/jbm4.10529
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发表时间：
2021-09
期刊：
影响因子：
3.8
通讯作者：
Clinkenbeard EL
中科院分区：
文献类型：
--
作者：
Edwards DF 3rd;Miller CJ;Quintana-Martinez A;Wright CS;Prideaux M;Atkins GJ;Thompson WR;Clinkenbeard EL
骨髓间充质祖细胞是多种细胞类型的前体，包括成骨细胞、脂肪细胞和软骨细胞。外部环境和信号对分化通路起指导作用。重要的是，衰老和慢性肾脏疾病等情况显示成骨细胞和脂肪细胞分化平衡的改变，对骨完整性产生不利影响。缺铁通常发生在衰老和慢性肾脏疾病期间，与骨密度降低有关。本研究的目的是评估缺铁对祖细胞分化途径能力的影响。小鼠和人类祖细胞，在标准成骨细胞和脂肪细胞方案下，在铁螯合剂去铁胺（DFO）的存在下分化。成骨条件下，5μM DFO显著损伤成骨细胞关键基因的表达，包括骨钙素、1型胶原和牙本质基质蛋白1。这导致碱性磷酸酶活性降低和矿化受损。尽管长期暴露于慢性缺铁环境中，细胞仍保持活力和正常的缺氧反应，并显著增加转铁蛋白受体和缺氧诱导因子1α的蛋白积累。当细胞维持在成脂条件下时，使用相似浓度的DFO。与成骨细胞分化相反，DFO在早期适度抑制过氧化物酶体增殖激活受体γ、脂蛋白脂肪酶和脂联素的脂肪细胞基因表达，并在后期恢复正常。脂质积累在所有条件下也相似。这些数据表明，铁在成骨细胞分化中至关重要，只要存在外部刺激，铁缺乏就不会阻碍脂肪形成。©2021作者。JBMR Plus由Wiley期刊有限责任公司代表美国骨骼和矿物研究协会出版。
Bone marrow mesenchymal progenitor cells are precursors for various cell types including osteoblasts, adipocytes, and chondrocytes. The external environment and signals act to direct the pathway of differentiation. Importantly, situations such as aging and chronic kidney disease display alterations in the balance of osteoblast and adipocyte differentiation, adversely affecting bone integrity. Iron deficiency, which can often occur during aging and chronic kidney disease, is associated with reduced bone density. The purpose of this study was to assess the effects of iron deficiency on the capacity of progenitor cell differentiation pathways. Mouse and human progenitor cells, differentiated under standard osteoblast and adipocyte protocols in the presence of the iron chelator deferoxamine (DFO), were used. Under osteogenic conditions, 5μM DFO significantly impaired expression of critical osteoblast genes, including osteocalcin, type 1 collagen, and dentin matrix protein 1. This led to a reduction in alkaline phosphatase activity and impaired mineralization. Despite prolonged exposure to chronic iron deficiency, cells retained viability as well as normal hypoxic responses with significant increases in transferrin receptor and protein accumulation of hypoxia inducible factor 1α. Similar concentrations of DFO were used when cells were maintained in adipogenic conditions. In contrast to osteoblast differentiation, DFO modestly suppressed adipocyte gene expression of peroxisome‐proliferating activated receptor gamma, lipoprotein lipase, and adiponectin at earlier time points with normalization at later stages. Lipid accumulation was also similar in all conditions. These data suggest the critical importance of iron in osteoblast differentiation, and as long as the external stimuli are present, iron deficiency does not impede adipogenesis. © 2021 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.