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Age-Related Increases in Marrow Fat Volumes have Regional Impacts on Bone Cell Numbers and Structure.
Calcified Tissue International ( IF 4.2 ) Pub Date : 2020-04-30 , DOI: 10.1007/s00223-020-00700-8
Ahmed Al Saedi 1, 2 , Lulu Chen 1, 3 , Steven Phu 1, 2 , Sara Vogrin 2 , Dengshun Miao 3 , Guylaine Ferland 4 , Pierrette Gaudreau 5 , Gustavo Duque 1, 2
Affiliation  

The increasing levels of bone marrow fat evident in aging and osteoporosis are associated with low bone mass and attributed to reduced osteoblastogenesis. Local lipotoxicity has been proposed as the primary mechanism driving this reduction in bone formation. However, no studies have examined the correlation between high levels of marrow fat volumes and changes in local cellularity. In this study, we hypothesize that areas of bone marrow with high fat volumes are associated with significant changes in cell number within a similar region of interest (ROI). Inbred albino Louvain (LOU) rats, originating from the Wistar strain, have been described as a model of healthy aging with the absence of obesity but expressing the typical features of age-related bone loss. We compared local changes in distal femur cellularity and structure in specific ROI of undecalcified bone sections from 4- and 20-month-old male and female LOU rats and Wistar controls. Our results confirmed that older LOU rats exhibited significantly higher fat volumes than Wistar rats (p < 0.001). These higher fat volume/total volume were associated with lower trabecular number (p < 0.05) and thickness (p < 0.05) and higher trabecular separation (p < 0.05). In addition, osteoblast and osteocyte numbers were reduced in the similar ROI containing high levels of adiposity, while osteoclast number was higher compared to control (p < 0.03). In summary, marrow ROIs with a high level of adiposity were associated with a lower bone mass and changes in cellularity explaining associated bone loss. Further studies assessing the levels of lipotoxicity in areas of high local marrow adiposity and identifying molecular actors involved in this phenomenon are still required.



中文翻译:

与年龄相关的骨髓脂肪量增加对骨细胞数量和结构具有区域性影响。

在衰老和骨质疏松症中明显增加的骨髓脂肪水平与骨量低有关,并归因于成骨细胞生成减少。已经提出局部脂毒性是驱动这种骨形成减少的主要机制。但是,尚无研究检查高水平的骨髓脂肪量与局部细胞密度变化之间的相关性。在这项研究中,我们假设高脂肪量的骨髓区域与相似目标区域(ROI)内的细胞数量发生重大变化有关。源自Wistar品系的近交白化病Louvain(LOU)大鼠已被描述为没有肥胖症的健康衰老模型,但具有与年龄相关的骨质流失的典型特征。我们比较了4个月和20个月大的雄性和雌性LOU大鼠和Wistar对照的未脱钙骨切片的股骨远端股骨头细胞结构和结构的局部变化。我们的结果证实,较老的LOU大鼠的脂肪量明显高于Wistar大鼠(p  <0.001)。这些较高的脂肪体积/总体积与较低的骨小梁数目(p  <0.05)和厚度(p  <0.05)和较高的骨小梁分离度(p  <0.05)相关。此外,在脂肪含量高的类似ROI中,成骨细胞和骨细胞的数量减少,而破骨细胞的数量则比对照组高(p  <0.03)。总之,具有高脂肪水平的骨髓ROI与较低的骨量和细胞变化有关,说明了相关的骨质流失。仍然需要进一步的研究来评估局部高脂肪性肥胖地区的脂毒性水平,并确定参与该现象的分子因子。

更新日期:2020-07-08
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