Nanostring-Based Identification of the Gene Expression Profile in Trigger Finger Samples.

Ravindra Kolhe,Sadanand Fulzele,Carlos M Isales,Umar Ghilzai,Pankaj Ahluwalia,Jie Chen,Mark Fulcher,Ashis K Mondal,Chetan Pundkar,Nikhil S Sahajpal

doi:10.3390/healthcare9111592

Ravindra Kolhe, Sadanand Fulzele + Show 8 more

Open Access

https://doi.org/10.3390/healthcare9111592

Copy DOI

Journal: Healthcare	Publication Date: Nov 20, 2021
Citations: 2	License type: CC BY 4.0

Affiliation: Augusta University, Auburn University

Abstract

Trigger finger is a common yet vastly understudied fibroproliferative hand pathology, severely affecting patients’ quality of life. Consistent trauma due to inadequate positioning within the afflicted finger’s tendon/pulley system leads to cellular dysregulation and eventual fibrosis. While the genetic characteristics of the fibrotic tissue in the trigger finger have been studied, the pathways that govern the initiation and propagation of fibrosis are still unknown. The complete gene expression profile of the trigger finger has never been explored. Our study has used the Nanostring nCounter gene expression assay to investigate the molecular signaling involved in trigger finger pathogenesis. We collected samples from patients undergoing trigger finger (n = 4) release surgery and compared the gene expression to carpal tunnel tissue (n = 4). Nanostring nCounter analysis identified 165 genes that were differentially regulated; 145 of these genes were upregulated, whereas 20 genes were downregulated. We found that several collagen genes were significantly upregulated, and a regulatory matrix metalloproteinase (MMP), MMP-3, was downregulated. Bioinformatic analysis revealed that several known signaling pathways were dysregulated, such as the TGF-β1 and Wnt signaling pathways. We also found several novel signaling pathways (e.g., PI3K, MAPK, JAK-STAT, and Notch) differentially regulated in trigger finger. The outcome of our study helps in understanding the molecular signaling pathway involved in the pathogenesis of the trigger finger.

Highlights

Trigger finger, known as stenosing tenosynovitis, is a musculoskeletal disorder in which a finger gets “locked” in either a flexed or extended position due to the disproportion between the diameter of that finger’s flexor tendon and pulley system
Basal production and degradation of collagen is a balanced equilibrium that ensures proper systemic functioning of the extracellular matrix (ECM) and body. This equilibrium is further maintained through the function of matrix metalloproteinase (MMP) enzymes that work to degrade various ECM proteins such as collagens, proteoglycans, and many other ECM components [31,32,33]
The downregulation of MMP-3 has wide-ranging effects that could potentially explain the vast build-up of collagen proteins in trigger finger [37]

Summary

Introduction

Known as stenosing tenosynovitis, is a musculoskeletal disorder in which a finger gets “locked” in either a flexed or extended position due to the disproportion between the diameter of that finger’s flexor tendon and pulley system. The most common symptom of this disorder is the “catching” of the finger in question in a flexed position, in addition to pain, clicking, and loss of motion in the finger. Not defined as a life-threatening condition, the pain and discomfort due to untreated trigger fingers are reported to cause significant debilitation for patients [6,7]. Treatment options of those suffering from trigger finger vary between noninvasive and invasive options, depending upon the severity of the condition. Studies have suggested that the best and most cost-effective treatment of trigger finger is an immediate surgical release or corticosteroid injections followed by an eventual surgical release [9]

Objectives

Methods

Conclusion