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REG-O3 chimeric peptide combining growth hormone and somatostatin sequences improves joint function and prevents cartilage degradation in rat model of traumatic knee osteoarthritis.
- Source :
-
PloS one [PLoS One] 2020 Apr 14; Vol. 15 (4), pp. e0231240. Date of Electronic Publication: 2020 Apr 14 (Print Publication: 2020). - Publication Year :
- 2020
-
Abstract
- Objective: REG-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.<br />Design: Osteoarthritis 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.<br />Results: ACLT/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.<br />Conclusion: This 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.<br />Competing Interests: SP and TN have declared that no competing interest exist. SE and YH received consultancy fees from REGULAXIS RM, RP and CV are employees and stockholders at REGULAXIS. CC is stockholder and CEO of REGULAXIS.
- Subjects :
- Animals
Anti-Inflammatory Agents, Non-Steroidal pharmacology
Cartilage, Articular pathology
Disease Models, Animal
Growth Hormone pharmacology
Knee Joint pathology
Male
Osteoarthritis, Knee etiology
Rats
Rats, Inbred Lew
Recombinant Fusion Proteins pharmacology
Somatostatin analogs & derivatives
Somatostatin pharmacology
Anterior Cruciate Ligament Injuries complications
Anti-Inflammatory Agents, Non-Steroidal therapeutic use
Cartilage, Articular drug effects
Growth Hormone therapeutic use
Knee Joint drug effects
Osteoarthritis, Knee drug therapy
Recombinant Fusion Proteins therapeutic use
Somatostatin therapeutic use
Subjects
Details
- Language :
- English
- ISSN :
- 1932-6203
- Volume :
- 15
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- PloS one
- Publication Type :
- Academic Journal
- Accession number :
- 32287299
- Full Text :
- https://doi.org/10.1371/journal.pone.0231240