Vaspin antagonizes high fat-induced bone loss in rats and promotes osteoblastic differentiation in primary rat osteoblasts through Smad-Runx2 signaling pathway

Hongwei Wang,Jiaxuan Li,Jin Xu,Mengqi Zhang,Fulian Chen,Yan Wang,Chunyan Jiang

doi:10.1186/s12986-020-0429-5

Hongwei Wang, Jiaxuan Li + Show 5 more

Open Access

https://doi.org/10.1186/s12986-020-0429-5

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Abstract

BackgroundVisceral 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.MethodsA 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.ResultsOur 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.ConclusionsOur results indicated that vaspin protects against HFD-induced bone loss, and promotes osteogenic differentiation by activating the Smad2/3-Runx2 signaling pathway.

Highlights

Osteoporosis and obesity are interrelated metabolic derangements, which are serious and prevalent health issues [1]
The rats were randomly separated into two groups: rats fed with normal diet (ND, n = 20) or high fat diet (HFD, n = 20, containing 60%kCal%fat, D12492, Research Diets, New Brunswick, NJ, USA) for 12 weeks to develop the control group and HFD-induced obesity (DIO) group
After rats were fed with high fat for 12 weeks, the body weight of HFD group was significantly higher than that of ND group (P < 0.05, Fig. 1b)

Summary

Introduction

Osteoporosis and obesity are interrelated metabolic derangements, which are serious and prevalent health issues [1]. Obesity tends to be accompanied by excessive consumption of HFD, and related to a chronic inflammation condition characterized by the increased plasma levels of proinflammatory cytokines such as tumor necrosis factor α (TNF-α), interleukin-6 (IL-6), and interleukin-1 (IL-1). These cytokines are known to stimulate the proliferation and differentiation of osteoclasts and might enhance bone resorption [9]. How vaspin influences bone formation and its underlying mechanisms in high fat-induced obese rats and rat primary osteoblasts (OBs) are not fully understood. The effects of vaspin on bone mechanical parameters and microarchitecture were evaluated

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