The Role of Wnt Pathway in the Pathogenesis of OA and Its Potential Therapeutic Implications in the Field of Regenerative Medicine

Author:

De Santis Maria1,Di Matteo Berardo23ORCID,Chisari Emanuele4ORCID,Cincinelli Gilberto1,Angele Peter5ORCID,Lattermann Christian6,Filardo Giuseppe7ORCID,Vitale Nicolò Danilo2,Selmi Carlo18ORCID,Kon Elizaveta23ORCID

Affiliation:

1. Division of Rheumatology and Clinical Immunology, Humanitas Research Hospital, Rozzano, Milan, Italy

2. Humanitas University Department of Biomedical Sciences, Via Manzoni 113, 20089 Rozzano, Milan, Italy

3. Humanitas Clinical and Research Center, Via Manzoni 56, 20089 Rozzano, Milan, Italy

4. Department of General Surgery and Medical Surgery Specialties, Section of Orthopaedics and Traumatology, University Hospital Policlinico-Vittorio Emanuele, University of Catania, Catania, Italy

5. Department of Trauma Surgery, University Medical Center Regensburg & Sporthopaedicum Straubing, Regensburg, Germany

6. Brigham and Women’s Hospital, Harvard Medical School, Chestnut Hill, MA, USA

7. Applied and Translational Research Center, IRCCS Istituto Ortopedico Rizzoli, Bologna, Italy

8. BIOMETRA Department, University of Milan, Milan, Italy

Abstract

Introduction. Osteoarthritis (OA) is a degenerative joint disease characterized by articular cartilage degradation, subchondral damage, and bone remodelling, affecting most commonly weight-bearing joints, such as the knee and hip. The loss of cartilage leads to joint space narrowing, pain, and loss of function which could ultimately require total joint replacement. The Wnt/β catenin pathway is involved in the pathophysiology of OA and has been proposed as a therapeutic target. Endogenous and pharmacological inhibitors of this pathway were recently investigated within innovative therapies including the use of platelet-rich plasma (PRP) and mesenchymal stem cells (MSCs). Methods. A review of the literature was performed on the PubMed database based on the following inclusion criteria: article written in English language in the last 20 years and dealing with (1) the role of Wnt-β catenin pathway in the pathogenesis of osteoarthritis and (2) pharmacologic or biologic strategies modulating the Wnt-β catenin pathway in the OA setting. Results. Evidences support that Wnt signalling pathway is likely linked to OA progression and severity. Its inhibition through natural antagonists and new synthetic or biological drugs shares the potential to improve the clinical condition of the patients by affecting the pathological activity of Wnt/β-catenin signalling. Conclusions. While further research is needed to better understand the mechanisms regulating the molecular interaction between OA regenerative therapies and Wnt, it seems that biologic therapies for OA exert modulation on Wnt/β catenin pathway that might be relevant in achieving the beneficial clinical effect of those therapeutic strategies.

Publisher

Hindawi Limited

Subject

General Immunology and Microbiology,General Biochemistry, Genetics and Molecular Biology,General Medicine

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