Wang Hongwei, Chen Fulian, Li Jiaxuan, Wang Yan, Jiang Chunyan, Wang Yan, Zhang Mengqi, Xu Jin
1Department of Endocrinology, Shandong Provincial Hospital affiliated to Shandong University, Jinan, Shandong People's Republic of China.
Shandong Provincial Key Laboratory of Endocrinology and Lipid Metabolism, Jinan, Shandong People's Republic of China.
Nutr Metab (Lond). 2020 Jan 22;17:9. doi: 10.1186/s12986-020-0429-5. eCollection 2020.
Visceral adipose tissue-derived serine protease inhibitor (vaspin), an adipose-derived hormone, exhibits various biological functions. Recently, studies showed that vaspin is closely related to bone metabolism. However, how vaspin influences bone formation and its underlying mechanisms in high fat-induced obese rats and rat primary osteoblasts (OBs) are not fully understood. In this study, the effects of vaspin on bone mechanical parameters and microarchitecture were evaluated.
A total of 40 male Sprague-Dawley (SD) rats at 5-week old were fed with high fat diet (HFD) and normal diet (ND) for 12 weeks followed by treatment of vaspin for 10 weeks. Micro CT and three-point bending tests were conducted to evaluate bone microstructure and biomechanics. The alkaline phosphatase (ALP) activity, expression of Runt-related transcription factor 2 (Runx2), Osterix (Osx), Collegen alpha1 (Colla1) procollagen I N-terminal peptide (PINP), C-telopeptide of type I collagen (CTX), Smad2/3 and p-Smad2/3 was detected by different methods.
Our data indicated that, compared with ND rats, HFD rats exhibited high body weight, decreased bone strength and deteriorative bone quality. In contrast, vaspin reduced the body weight, improved the whole body metabolic status, enhanced bone strength, trabecular bone mass, and expression of Runx2, Osx, PINP, and decreased the expression level of plasma CTX. In vitro studies showed that vaspin promoted osteogenic differentiation and ALP activity in rat primary OBs in a dose dependent manner. Vaspin also upregulated mRNA expression of osteogenesis-related genes Runx2, Osx and Colla1 and protein expression of Runx2, Smad2/3 and p-Smad2/3.
Our results indicated that vaspin protects against HFD-induced bone loss, and promotes osteogenic differentiation by activating the Smad2/3-Runx2 signaling pathway
内脏脂肪组织衍生的丝氨酸蛋白酶抑制剂（vaspin）是一种脂肪衍生激素，具有多种生物学功能。最近，研究表明vaspin与骨代谢密切相关。然而，vaspin如何影响高脂肪诱导的肥胖大鼠和大鼠原代成骨细胞（OBs）的骨形成及其潜在机制尚未完全明确。在本研究中，评估了vaspin对骨力学参数和微观结构的影响。
选取40只5周龄雄性Sprague-Dawley（SD）大鼠，给予高脂饮食（HFD）和正常饮食（ND）12周，随后给予vaspin治疗10周。进行显微CT和三点弯曲试验以评估骨微观结构和生物力学。采用不同方法检测碱性磷酸酶（ALP）活性、 runt相关转录因子2（Runx2）、osterix（Osx）、胶原蛋白α1（Colla1）、前胶原I N端肽（PINP）、I型胶原C端肽（CTX）、Smad2/3和p-Smad2/3的表达。
我们的数据表明，与ND大鼠相比，HFD大鼠体重增加、骨强度降低且骨质恶化。相反，vaspin降低了体重，改善了全身代谢状态，增强了骨强度、小梁骨量以及Runx2、Osx、PINP的表达，并降低了血浆CTX的表达水平。体外研究表明，vaspin以剂量依赖的方式促进大鼠原代OBs的成骨分化和ALP活性。Vaspin还上调了成骨相关基因Runx2、Osx和Colla1的mRNA表达以及Runx2、Smad2/3和p-Smad2/3的蛋白表达。
我们的结果表明，vaspin可预防HFD诱导的骨质流失，并通过激活Smad2/3-Runx2信号通路促进成骨分化
