Expression of PAPP-A2 and IGF Pathway-Related Proteins in the Hip Joint of Normal Rat and Those with Developmental Dysplasia of the Hip.

Yufan Chen,Enbo Wang,Lijun Zhang,Haixiang Lv,Lianyong Li,Qun Zhao

doi:10.1155/2019/7691531

Abstract

Developmental dysplasia of the hip (DDH) is one of the major causes of child disability and early osteoarthritis. Genetic factors play an important role, but which still remain unclear. Pregnancy-associated plasma protein-A2 (PAPP-A2), a special hydrolase of insulin-like growth factor binding protein-5 (IGFBP-5), has been confirmed to be associated with DDH by previous studies. The aim of this study was firstly, to investigate the expression of PAPP-A2 and insulin-like growth factor (IGF) pathway-related proteins in normal rat's hip joints; secondly, to compare the variations of those proteins between DDH model rats and normal ones. The DDH model was established by swaddling the rat's hind legs in hip adduction and extension position. The hip joints were collected for expression study of fetal rats, normal newborn rats, and DDH model rats. Positive expression of PAPP-A2 and IGF pathway-related proteins was observed in all the hip joints of growing-stage rats. Ultimately, IGF1 was downregulated; insulin-like growth factor 1 receptor (IGF1R) showed an opposite trend in DDH rats when compared with normal group. The PAPP-A2 and IGF pathway-associated proteins may also be involved in the development of the rat's hip joint, which bring the foundation for further revealing the pathogenic mechanism of DDH.

Highlights

Developmental dysplasia of the hip (DDH) is an important cause of childhood disability, which can predispose a child to early onset degenerative changes and painful arthritis [1]
The main goals of our study are to confirm the expression of plasma protein-A2 (PAPP-A2), insulin-like growth factor binding protein-5 (IGFBP-5), insulin-like growth factor 1 receptor (IGF1R), and IGF1 in the rat hip during different developmental stages and to examine the different expressions in the hips of normal rats and DDH model rats
Gapdh was used as a standardizing sample, since its mRNA levels did not change between different time phases.Pappa2, Igf1, and Igf1R transcript levels showed the same trends

Summary

Introduction

Developmental dysplasia of the hip (DDH) is an important cause of childhood disability, which can predispose a child to early onset degenerative changes and painful arthritis [1]. DDH is characterized by a rough joint surface, cystic degeneration, and deformation of the femoral head in the severe stage [2]. It affects approximately 1 to 5 per 1,000 newborns, among which about eighty percent are females. The etiology of DDH is complex and still unclear. Factors contributing to DDH include breech presentation, female sex, firstborn status, and oligohydramnios [3]. Gene association mapping studies have hitherto identified several susceptible genes of DDH [4]. Mutations of cartilage formation-related proteins are associated with DDH [2]

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