Upregulation of cGMP‐dependent Protein Kinase (PRKG1) in the Development of Adolescent Idiopathic Scoliosis

Abstract

Objective To explore the molecular regulatory mechanisms underlying fibroblast differentiation and dysfunction in the development of adolescent idiopathic scoliosis (AIS) in an effort to identify candidate therapeutic targets for AIS. Methods The GSE110359 dataset, obtained from the bone marrow stromal cells of 12 AIS patients and five healthy controls, was retrieved from the GEO database. The data were preprocessed and differentially expressed genes (DEGs) were identified. KEGG pathway and Gene Ontology (GO)‐Biological Process (BP) enrichment analyses were performed to identify the function of the DEGs. A protein–protein interaction (PPI) and a microRNA‐transcription factor (TF)‐target co‐regulatory network were constructed to identify hub genes in the development of AIS. In addition, hub DEGs were evaluated by quantitative PCR (qPCR) and immunohistochemical staining. Results A total of 188 DEGs including 100 up‐regulated and 88 down‐regulated genes were obtained. The up‐regulated DEGs were related to “p53 signaling pathway”, “FoxO signaling pathway”, and “cGMP‐PKG signaling pathway” terms, while the down‐regulated DEGs were significantly enriched in seven terms including “protein processing in endoplasmic reticulum”. The key up‐regulated genes, PRKG1, CCNG2, and KAT2B, and the key down‐regulated genes, MAP2K1 and DUSP6, were identified by the PPI and miRNA‐TF‐Target regulatory network analyses. mRNA expression patterns for PRKG1, DUSP6, and KAT2B were successfully verified by qPCR. In addition, PRKG1 protein levels were found to be elevated during the immunohistochemical analysis. Conclusion Increased expression of PRKG1 in AIS patients might be an attractive therapeutic target for AIS. However, further gain or loss‐of‐function studies should be conducted.

What is New in Pediatric Orthopaedic: Basic Science

“…Previous studies have examined several genes in the fibroblast differentiation pathway as candidate genes for developing scoliosis 16,17. Examination of the molecular regulatory mechanism underlying fibroblast differentiation found upregulation of cGMP dependent protein kinase gene, PRKG1 , which has been identified as a novel negative regulator of osteoblast differentiation 18…”

“…16,17 Examination of the molecular regulatory mechanism underlying fibroblast differentiation found upregulation of cGMP dependent protein kinase gene, PRKG1, which has been identified as a novel negative regulator of osteoblast differentiation. 18 Abnormal myogenesis has also been implicated in the development of AIS. Muscle asymmetry between the concavity and convexity of a scoliotic curve is observed clinically.…”

BMP6 participates in the pathogenesis of adolescent idiopathic scoliosis by regulating osteopenia

“…In patients with AIS, the expression of CGMP-dependent protein kinase (PRKG1) is upregulated. PRKG1 plays a role in the CGMP-PKG signaling pathway and has been identified as a new negative regulator of osteoblast differentiation in BMSCs (Hou et al, 2020). GPR126 is asymmetrically expressed in the convex/concave spine of patients with AIS.…”

Rare Causes of Arterial Hypertension and Thoracic Aortic Aneurysms—A Case-Based Review

“…Scoliosis is not an infrequent finding, and it was present in our patient as well ( Table 1 ). Of interest, PRKG1 is a novel negative regulator of osteoblast differentiation in human skeletal stem cells, and PRKG1 was found to have increased expression in idiopathic scoliosis, where it may become a therapeutic target [ 36 , 37 ].…”