Passin Vanessa, Ledesma-Colunga Maria G, Baschant Ulrike, Hofbauer Lorenz C, Rauner Martina
Department of Medicine III and Center for Healthy Aging, Medical Faculty and University Hospital Carl Gustav Carus, Dresden University of Technology, 01307 Dresden, Germany.
JBMR Plus. 2025 May 23;9(7):ziaf069. doi: 10.1093/jbmrpl/ziaf069. eCollection 2025 Jul.
Transferrin receptor 1 (Tfr1) plays a key role in mediating the cellular uptake of transferrin-bound iron. While Tfr1 is essential for iron uptake in erythroid cells and skeletal muscle, it is dispensable for iron acquisition in hepatocytes, intestinal epithelial, or endothelial cells. In this study, we investigated the significance of Tfr1 for iron uptake and cellular function in bone-forming osteoblasts. Therefore, we examined the bone characteristics of male and female Tfr1;Osx:cre (osteoprogenitors) conditional KO mice at 12 and 24 wk of age. Bone marrow-derived cells from Tfr1;Osx:cre mice were differentiated into osteoblasts in vitro to assess cellular iron status as well as cellular differentiation and function. Our findings indicate that Tfr1 deficiency in osteoprogenitors in male mice resulted in increased trabecular bone mass in the axial skeleton with decreased bone formation rate as well as decreased levels of serum bone turnover markers. Despite increased bone mass in the femur in females resulting from Tfr1 deficiency in osteoprogenitors, loss of bone mass following ovariectomy was not mitigated. Transferrin receptor 1-deficient osteoblasts showed mild changes in cytosolic iron levels and decreased mineralization. These results suggest a minor role of Tfr1 in osteoblasts differentiation and function but highlight distinct strategies for iron acquisition employed by bone cells to maintain cellular iron homeostasis.
转铁蛋白受体1（Tfr1）在介导细胞摄取与转铁蛋白结合的铁过程中发挥关键作用。虽然Tfr1对红细胞和骨骼肌摄取铁至关重要，但对于肝细胞、肠上皮细胞或内皮细胞获取铁而言并非必需。在本研究中，我们调查了Tfr1对成骨细胞中铁摄取和细胞功能的重要性。因此，我们检测了12周龄和24周龄的雄性和雌性Tfr1;Osx:cre（骨祖细胞）条件性敲除小鼠的骨骼特征。将来自Tfr1;Osx:cre小鼠的骨髓来源细胞在体外分化为成骨细胞，以评估细胞铁状态以及细胞分化和功能。我们的研究结果表明，雄性小鼠骨祖细胞中Tfr1缺乏导致中轴骨骼小梁骨量增加，骨形成率降低，血清骨转换标志物水平下降。尽管雌性小鼠由于骨祖细胞中Tfr1缺乏导致股骨骨量增加，但卵巢切除术后的骨量丢失并未得到缓解。转铁蛋白受体1缺陷的成骨细胞在胞质铁水平上有轻微变化，矿化减少。这些结果表明Tfr1在成骨细胞分化和功能中作用较小，但突出了骨细胞为维持细胞铁稳态所采用的不同铁获取策略。
