Disturbed bone marrow adiposity in patients with Cushing's syndrome and glucocorticoid- and postmenopausal- induced osteoporosis.
Disturbed bone marrow adiposity in patients with Cushing's syndrome and glucocorticoid- and postmenopausal- induced osteoporosis.
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DOI：
10.3389/fendo.2023.1232574
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发表时间：
2023
影响因子：
5.2
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中科院分区：
文献类型：
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骨髓中的骨骼肌干/祖细胞（SSPC）可以响应微环境信号输入（包括激素信号）分化为成骨细胞或脂肪细胞。糖皮质激素（GC）是一种促进脂肪形成分化的皮质类固醇激素，在库欣综合征（CS）患者中内源性增加。在这里，我们调查骨髓肥胖的变化，响应内源性或外源性GC增加。为此，我们将CS患者和绝经后糖皮质激素诱导的骨质疏松症（GC-O）妇女的骨活检与年龄匹配的对照组（包括绝经后骨质疏松症患者（PM-O））进行比较。分析了CS患者和健康对照组，以及绝经后GC-O女性和匹配对照组的髂嵴骨活检;另一个队列包括PM-O女性的活检。将塑料包埋的活检切片用于脂肪细胞的组织形态学表征和定量。测定每个组织的脂肪细胞面积分数（Ad.Ar/T.Ar）和骨髓面积分数（Ad.Ar/Ma.Ar）、平均脂肪细胞轮廓面积（Ad.Pf.Ar）和脂肪细胞轮廓密度（N.Ad.Pf/Ma.Ar），并与类固醇水平相关。此外，脂肪细胞的空间分布相对于骨小梁的特点和骨髓肥胖和骨重建参数之间的相关性进行了研究。CS和GC-O患者的活检显示Ad.Ar/Ma.Ar增加，沿着脂肪细胞肥大和增生。CS患者的Ad.Ar/Ma.Ar和Ad.Pf.Ar均与血清皮质醇水平显著相关。空间分布分析显示，在CS中，靠近骨小梁（<100 µm）的Ad.Ar/Ma.Ar的增加由脂肪细胞肥大和增生介导，而进一步进入骨髓（>100 µm）的N.Ad.Pf/Ma.Ar保持不变。相比之下，GC-O患者仅表现出增加的Ad.Ar/Ma.Ar和骨小梁表面的平均Ad.Pf.Ar>100 µm，突出了内源性类固醇蓄积增加的差异效应。最后，Ad.Ar/Ma.Ar和Ad.Ar/T.Ar与冠层覆盖度相关。CS患者皮质醇产生增加可诱导骨髓肥胖增加，主要由脂肪细胞肥大介导。这种肥胖在骨小梁表面附近特别明显，在那里也发生增生。CS和GC-O患者肥胖的差异模式突出了骨髓脂肪细胞及其祖细胞在这两种GC介导的骨病中的反应可能不同。
Skeletal stem/progenitor cells (SSPCs) in the bone marrow can differentiate into osteoblasts or adipocytes in response to microenvironmental signalling input, including hormonal signalling. Glucocorticoids (GC) are corticosteroid hormones that promote adipogenic differentiation and are endogenously increased in patients with Cushing´s syndrome (CS). Here, we investigate bone marrow adiposity changes in response to endogenous or exogenous GC increases. For that, we characterize bone biopsies from patients with CS and post-menopausal women with glucocorticoid-induced osteoporosis (GC-O), compared to age-matched controls, including postmenopausal osteoporotic patients (PM-O). Transiliac crest bone biopsies from CS patients and healthy controls, and from postmenopausal women with GC-O and matched controls were analysed; an additional cohort included biopsies from women with PM-O. Plastic-embedded biopsies were sectioned for histomorphometric characterization and quantification of adipocytes. The fraction of adipocyte area per tissue (Ad.Ar/T.Ar) and marrow area (Ad.Ar/Ma.Ar), mean adipocyte profile area (Ad.Pf.Ar) and adipocyte profile density (N.Ad.Pf/Ma.Ar) were determined and correlated to steroid levels. Furthermore, the spatial distribution of adipocytes in relation to trabecular bone was characterized and correlations between bone marrow adiposity and bone remodeling parameters investigated. Biopsies from patients with CS and GC-O presented increased Ad.Ar/Ma.Ar, along with adipocyte hypertrophy and hyperplasia. In patients with CS, both Ad.Ar/Ma.Ar and Ad.Pf.Ar significantly correlated with serum cortisol levels. Spatial distribution analyses revealed that, in CS, the increase in Ad.Ar/Ma.Ar near to trabecular bone (<100 µm) was mediated by both adipocyte hypertrophy and hyperplasia, while N.Ad.Pf/Ma.Ar further into the marrow (>100 µm) remained unchanged. In contrast, patients with GC-O only presented increased Ad.Ar/Ma.Ar and mean Ad.Pf.Ar>100 µm from trabecular bone surface, highlighting the differential effect of increased endogenous steroid accumulation. Finally, the Ad.Ar/Ma.Ar and Ad.Ar/T.Ar correlated with the canopy coverage above remodeling events. Increased cortisol production in patients with CS induces increased bone marrow adiposity, primarily mediated by adipocyte hypertrophy. This adiposity is particularly evident near trabecular bone surfaces, where hyperplasia also occurs. The differential pattern of adiposity in patients with CS and GC-O highlights that bone marrow adipocytes and their progenitors may respond differently in these two GC-mediated bone diseases.
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影响因子：
12.4
作者：
Chen Q;Shou P;Zheng C;Jiang M;Cao G;Yang Q;Cao J;Xie N;Velletri T;Zhang X;Xu C;Zhang L;Yang H;Hou J;Wang Y;Shi Y
通讯作者：
Shi Y
影响因子：
4
作者：
Dang, T.;Faje, A. T.;Meenaghan, E.;Bredella, M. A.;Bouxsein, M. L.;Klibanski, A.;Fazeli, P. K.
通讯作者：
Fazeli, P. K.
影响因子：
3.7
作者：
Ferrau, Francesco;Giovinazzo, Salvatore;Cannavo, Salvatore
通讯作者：
Cannavo, Salvatore
影响因子：
6.2
作者：
Briot K;Roux C
通讯作者：
Roux C
影响因子：
5.8
作者：
Bredella, Miriam A.;Fazeli, Pouneh K.;Klibanski, Anne
通讯作者：
Klibanski, Anne