慢性阻塞性肺疾病卵巢完整大鼠和去卵巢大鼠的骨质流失和骨髓脂肪增加。

IF 3.5 2区 医学 Q1 Medicine
Jingzheng Fan, Yuyan Jiang, Lechang Yu, Xu Lu, Qiang Zhang
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引用次数: 0

摘要

目的:骨质疏松症是慢性阻塞性肺疾病(COPD)患者可能出现的一种重要的临床显著肺外合并症。虽然有报道称骨髓脂肪与骨完整性呈负相关,但这种脂肪在copd诱导的骨质流失中的作用尚不清楚。本研究的目的是阐明COPD如何影响卵巢完整和卵巢切除(OVX)大鼠的骨骼和骨髓脂肪。方法:本研究使用32只5月龄雌性Wistar大鼠进行双侧OVX或假手术。术后第7天开始,这些大鼠定期暴露于香烟烟雾(CS)或室内空气(RA)中5个月。在基线、3个月和5个月时,通过水/脂肪MRI和双能x线吸收仪测量左股骨近端和L4-L5椎的骨髓脂肪分数(FF)和骨矿物质密度(BMD)等一系列参数。此外,我们还分析了肺功能、肺形态、组织病理学检测的骨髓脂肪细胞特征、显微ct扫描检测的骨小梁微结构特征、qPCR检测的成脂和成骨标志物基因表达变化以及ELISA检测的血清骨转换生物标志物水平。结果:CS暴露5个月后,卵巢完整大鼠和OVX大鼠骨髓脂肪扩张明显加剧,整体骨质恶化。与RA暴露的大鼠相比,CS暴露的大鼠表现出:(1)骨髓FF增高,骨髓脂肪细胞直径增大,脂肪细胞密度增大,脂肪细胞体积百分比增大;(2)骨髓中脂肪生成基因PPARγ2、FABP4的表达增加;(3)骨小梁微结构恶化,骨密度降低,成骨基因表达水平降低(Runx2),血清骨生物标志物水平变化,包括骨形成标志物水平降低和骨吸收标志物水平升高。与单独暴露于CS相比,慢性CS暴露和OVX的组合与骨髓中更明显的脂肪扩张和骨质流失相关。随着时间的推移,CS暴露与骨髓中脂肪的进行性积累和骨组织的恶化有关,CS暴露后3个月内骨髓FF显著不同,而BMD在第5个月相对于ra暴露的对照大鼠显着下降。结论:这些结果表明,在COPD模型中,骨髓脂肪与雌性大鼠骨质疏松症的发生密切相关,可能对成骨细胞和破骨细胞的活性都有影响。这些结果强调了在寻求更有效地管理COPD患者骨质疏松症时靶向骨髓脂肪细胞的重要性。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Bone loss and increased bone marrow adiposity in ovary-intact and ovariectomized rats with chronic obstructive pulmonary disease.

Objective: Osteoporosis is a major clinically significant extrapulmonary comorbidity that can arise in individuals with chronic obstructive pulmonary disease (COPD). While there have been reports of a negative correlation between bone marrow adiposity and bone integrity, the role of such adiposity in COPD-induced bone loss is not well understood. This study was developed with the aim of clarifying how COPD affects bone and bone marrow fat in both ovary-intact and ovariectomized (OVX) rats.

Methods: This study utilized 32 five-month-old female Wistar rats that either underwent bilateral OVX or Sham surgical procedures. Beginning 7 days after surgery, these rats were regularly exposed to cigarette smoke (CS) or room air (RA) for 5 months. At baseline, 3 months, and 5 months, a series of parameters were analyzed including the bone marrow fat fraction (FF) and bone mineral density (BMD) for the left proximal femur and L4-L5 vertebrae, as measured through water/fat MRI and dual-energy X-ray absorptiometry. Moreover, pulmonary function, lung morphometry, marrow adipocyte characteristics detected via histopathology, trabecular bone microarchitectural features detected by micro-CT scanning, changes in adipogenic and osteogenic marker gene expression detected by qPCR, and serum levels of bone turnover biomarkers detected by ELISA were also analyzed.

Results: CS exposure for 5 months was associated with the significant exacerbation of fat expansion in the bone marrow together with overall bone deterioration in the ovary-intact and OVX rats. Relative to rats exposed to RA, those exposed to CS presented with: (1) Increased marrow FF, larger marrow adipocyte diameter, greater adipocyte density, and a higher adipocyte volume percentage; (2) an increase in the expression of adipogenic genes (PPARγ2, FABP4) in the bone marrow; (3) trabecular bone microstructural deterioration, reduced BMD, lower levels of osteogenic gene expression (Runx2), and changes in the levels of serum bone biomarkers including decreased bone formation marker levels together with increased levels of markers of bone resorption. The combination of chronic CS exposure and OVX was associated with even more pronounced fat expansion in the bone marrow and bone loss relative to CS exposure in isolation. Over time, CS exposure was associated with the progressive accumulation of fat in the bone marrow and the deterioration of bone tissue, with marrow FF differing significantly within 3 months of CS exposure, while BMD was significantly decreased by month 5 relative to RA-exposed control rats.

Conclusion: These results suggest that bone marrow adiposity is closely associated with the onset of osteoporosis among female rats in this model of COPD, with likely effects on the activity of both osteoblasts and osteoclasts. These results underscore the importance of targeting adipose cells in the bone marrow when seeking to more effectively manage osteoporosis among patients with COPD.

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来源期刊
Journal of Endocrinological Investigation
Journal of Endocrinological Investigation ENDOCRINOLOGY & METABOLISM-
CiteScore
8.10
自引率
7.40%
发文量
242
期刊介绍: The Journal of Endocrinological Investigation is a well-established, e-only endocrine journal founded 36 years ago in 1978. It is the official journal of the Italian Society of Endocrinology (SIE), established in 1964. Other Italian societies in the endocrinology and metabolism field are affiliated to the journal: Italian Society of Andrology and Sexual Medicine, Italian Society of Obesity, Italian Society of Pediatric Endocrinology and Diabetology, Clinical Endocrinologists’ Association, Thyroid Association, Endocrine Surgical Units Association, Italian Society of Pharmacology.
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