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

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.

Dipeptidyl peptidase-4 is associated with myogenesis in patients with adolescent idiopathic scoliosis possibly via mediation of insulin sensitivity

“…As documented in earlier literatures, abnormal metabolism has been implicated in the etiology of AIS. To characterize the role of DPP-4 in the metabolism of AIS patients, Normand et al [ 14 ] firstly isolated osteoblast from AIS patients and controls and reported abnormally down-regulated expression of DPP-4 in AIS patients. In the current study, we successfully validated that AIS subjects had remarkably lower DPP-4 expression in both serum and paraspinal muscles when compared with the controls.…”

“…DPP-4 inhibitor, launched and wildly used in clinical practice, was proven to improve BMD and decrease the risk of fracture in type 2 diabetes, establishing a relationship between DPP-4 and bone quality [ 13 ]. Normand et al [ 14 ] observed lower serum expression of DPP-4 in AIS patients. Moreover, remarkable differences in DPP-4 activity and regulation between osteoblasts of AIS patients and healthy controls were found in their study.…”

Etiology of Adolescent Idiopathic Scoliosis: A Literature Review

“…GLP-1 increases insulin release in the pancreas, enhancing insulin response with bone growth during adolescent development. This further explains the increased prevalence of AIS in individuals with lower BMI values [43,44].…”

A Differential Hypofunctionality of Gαi Proteins Occurs in Adolescent Idiopathic Scoliosis and Correlates with the Risk of Disease Progression

“…Melatonin binds to melatonin receptors that are coupled to Gαi proteins and blocks the synthesis of cAMP produced by adenylate cyclases. We hypothesized that Gαi protein impairment could explain the melatonin-signaling pathway dysfunction 10 and other neuroendocrine abnormalities observed in AIS 11–13 . We tested Gi-coupled receptor signaling using peripheral blood mononuclear cells (PBMCs) of AIS patients using cellular dielectric spectroscopy (CDS) 14 .…”