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

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

doi:10.1186/s12986-020-0429-5

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

Nutr Metab (Lond). 2020 Jan 22:17:9. doi: 10.1186/s12986-020-0429-5. eCollection 2020.

Authors

Hongwei Wang^{1

2

3

4}, Fulian Chen^{1

2

3

5}, Jiaxuan Li^{1

2

3}, Yan Wang^{1

2

3

6}, Chunyan Jiang^{1

2

3

7}, Yan Wang^{1

2

3}, Mengqi Zhang^{1

2

3}, Jin Xu^{1

2

3}

Affiliations

¹ 1Department of Endocrinology, Shandong Provincial Hospital affiliated to Shandong University, Jinan, Shandong People's Republic of China.
² Shandong Provincial Key Laboratory of Endocrinology and Lipid Metabolism, Jinan, Shandong People's Republic of China.
³ Institute of Endocrinology and Metabolism, Shandong Academy of Clinical Medicine, Jinan, Shandong 250021 People's Republic of China.
⁴ 4Department of Clinical Nutrition, People's Hospital of Rizhao, Rizhao, Shandong 276800 People's Republic of China.
⁵ 5Department of Endocrinology, Affiliated Yidu Central Hospital of Weifang Medical College, Weifang, Shandong 272500 People's Republic of China.
⁶ Department of Endocrinology, The Second Affiliated Hospital of Shandong First Medical University, Tai'an, Shandong 271000 People's Republic of China.
⁷ Department of Endocrinology, People's Hospital of Linyi, Linyi, Shandong 276000 People's Republic of China.

Abstract

Background: 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.

Methods: 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.

Results: 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.

Conclusions: Our results indicated that vaspin protects against HFD-induced bone loss, and promotes osteogenic differentiation by activating the Smad2/3-Runx2 signaling pathway.

Keywords: High fat diet; Osteogenic differentiation; P-Smad2/3; Runx2; Smad2/3; Vaspin.