REG-O3 chimeric peptide combining growth hormone and somatostatin sequences improves joint function and prevents cartilage degradation in rat model of traumatic knee osteoarthritis.

Rodrick Montjean,Yves Henrotin,Claude Carelli,Sonia Escaich,Raffaello Paolini,Christelle Vêtu,Sébastien Pirson,Thibaut Neutelings

doi:10.1371/journal.pone.0231240

Rodrick Montjean, Yves Henrotin + Show 6 more

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https://doi.org/10.1371/journal.pone.0231240

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Journal: PloS one	Publication Date: Apr 14, 2020
Citations: 6	License type: CC BY 4.0

Affiliation: University of Liège

Abstract

ObjectiveREG-O3 is a 24-aminoacid chimeric peptide combining a sequence derived from growth hormone (GH) and an analog of somatostatin (SST), molecules displaying cartilage repair and anti-inflammatory properties, respectively. This study aimed to investigate the disease-modifying osteoarthritis drug (DMOAD) potential of REG-O3 by analyzing its effect on pain, joint function and structure, upon injection into osteoarthritic rat knee joint.DesignOsteoarthritis was induced in the right knee of mature male Lewis rats (n = 12/group) by surgical transection of the anterior cruciate ligament (ACLT) combined with partial medial meniscectomy (pMMx). Treatments were administered intra-articularly from fourteen days after surgery through three consecutive injections one week apart. The effect of REG-O3, solubilized in a liposomal solution and injected at either 5, 25 or 50 μg/50 μL, was compared to liposomal (LIP), dexamethasone and hyaluronic acid (HA) solutions. The study endpoints were the pain/function measured once a week throughout the entire study, and the joint structure evaluated eight weeks after surgery using OARSI score.ResultsACLT/pMMx surgery induced a significant modification of weight bearing in all groups. When compared to liposomal solution, REG-O3 was able to significantly improve weight bearing as efficiently as dexamethasone and HA. REG-O3 (25 μg) was also able to significantly decrease OARSI histological global score as well as degeneration of both cartilage and matrix while the other treatments did not.ConclusionThis study provides evidence of a remarkable protecting effect of REG-O3 on pain/knee joint function and cartilage/matrix degradation in ACLT/pMMx model of rat osteoarthritis. REG-O3 thus displays an interesting profile as a DMOAD.

Highlights

Osteoarthritis (OA), one major issue in public health due to the wide proportion of the affected population [1,2], lacks disease-modifying treatment
This study provides evidence of a remarkable protecting effect of REG-O3 on pain/knee joint function and cartilage/matrix degradation in anterior cruciate ligament (ACLT)/pMMx model of rat osteoarthritis
The cytokinesis-block proliferation index (CBPI) quantification, replication index (RI) and micronuclei induction in V79-4 cell lines grown were observed with increasing concentrations of REG-O3 (S1 Appendix, method)

Summary

Introduction

Osteoarthritis (OA), one major issue in public health due to the wide proportion of the affected population [1,2], lacks disease-modifying treatment. The commonly used pharmaceutical treatments for OA, including acetaminophen, nonsteroidal anti-inflammatory drugs and intra-articular injection of corticoids and hyaluronic acid (HA), only focus on symptoms [3,4,5,6,7]. Even for these intra-articular (IA) injections, whose symptomatic effects were documented in precise indication, there is no consensus on their potential disease-modifying activities. Many growth factors and hormones have been studied as putative therapeutic molecules for articular defects due to their crucial role in the control of cartilage homeostasis [8]. A clinical study has shown that adding GH to platelet rich plasma for IA injection improved function of the osteoarthritic knee joint in a short period of time [14]

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Conclusion