Dipeptidyl Peptidase-4 and Adolescent Idiopathic Scoliosis: Expression in Osteoblasts

Emilie Normand,Anita Franco,Valérie Marcil,Alain Moreau

doi:10.1038/s41598-017-03310-x

Abstract

It has been proposed that girls with adolescent idiopathic scoliosis (AIS) tend to have a taller stature and a lower body mass index. Energy homeostasis, that is known to affect bone growth, could contribute to these characteristics. In circulation, dipeptidyl peptidase-4 (DPP-4) inactivates glucagon-like peptide-1 (GLP-1), an incretin that promotes insulin secretion and sensitivity. Our objectives were to investigate DPP-4 status in plasma and in osteoblasts of AIS subjects and controls and to evaluate the regulatory role of metabolic effectors on DPP-4 expression. DPP-4 activity was assessed in plasma of 113 girls and 62 age-matched controls. Osteoblasts were isolated from bone specimens of AIS patients and controls. Human cells were incubated with glucose, insulin, GLP-1 and butyrate. Gene and protein expressions were evaluated by RT-qPCR and Western blot. Our results showed 14% inferior plasma DPP-4 activity in AIS patients when compared to healthy controls (P = 0.0357). Similarly, osteoblasts derived from AIS subjects had lower DPP-4 gene and protein expression than controls by 90.5% and 57.1% respectively (P < 0.009). DPP-4 expression was regulated in a different manner in osteoblasts isolated from AIS participants compared to controls. Our results suggest a role for incretins in AIS development and severity.

Highlights

It has been proposed that girls with adolescent idiopathic scoliosis (AIS) tend to have a taller stature and a lower body mass index
Others revealed that a polymorphism in the leptin receptor (LEPR) gene was associated with the occurrence of AIS, supporting the idea that malfunctions in the leptin signalling pathway could contribute to AIS development[15]
While 2 h incubations with glucagon-like peptide-1 (GLP-1) did not impact dipeptidyl peptidase-4 (DPP-4) expression (Supplementary Figure 6), we found that the 24 h treatment had an effect on gene expression in cells obtained from controls without affecting protein levels (Fig. 5)

Summary

Introduction

It has been proposed that girls with adolescent idiopathic scoliosis (AIS) tend to have a taller stature and a lower body mass index. Osteoblasts derived from AIS subjects had lower DPP-4 gene and protein expression than controls by 90.5% and 57.1% respectively (P < 0.009). Several studies have shown that girls with AIS tend to have different anthropometric features compared to age-matched controls such as a taller stature, lower body mass index and systemic low bone mass, but the causes of these differences remain unexplained[3,4,5]. In addition to adipokines secreted by the adipose tissue, the gastro-intestinal (GI) tract secretes peptides in response to nutrient intake[18] These incretins modulate glucose homeostasis, mainly through glucose-induced insulin secretion, inhibition of glucagon release and enhancement of insulin sensitivity[19], but accumulating evidence suggests that they may influence bone metabolism[20, 21]. New evidences indicate that short-chain fatty acids including butyric acid, that are products of non-digestible carbohydrate fermentation by gut microbiota, can stimulate GLP-1 secretion, thereby influencing glucose homeostasis and energy balance[24, 25] and supporting the role of gut microbiota in bone health[26, 27]

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Conclusion