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Biomedicines
Volume 12
Issue 10
10.3390/biomedicines12102292
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Review

The Pathogenetic Role of RANK/RANKL/OPG Signaling in Osteoarthritis and Related Targeted Therapies

by
Gabriele Di Cicco
1,
Emanuela Marzano
1,
Andrea Mastrostefano
1,
Dario Pitocco
2,
Rodrigo Simões Castilho
3,
Roberto Zambelli
3,
Antonio Mascio
4,5,
Tommaso Greco
5,6,
Virginia Cinelli
4,5,
Chiara Comisi
4,5,*,
Giulio Maccauro
4,5 and
Carlo Perisano
4,5
1
Department of Physiology and Pharmacology, Sapienza University of Rome, 00185 Rome, Italy
2
Diabetes Care Unit, Endocrinology, University Hospital “A. Gemelli”, Catholic University of the Sacred Heart, 00136 Rome, Italy
3
Department of Orthopaedics and Traumatology, Mater Dei Hospital, Belo Horizonte 30170-041, Brazil
4
Department of Orthopedics and Geriatric Sciences, Catholic University of the Sacred Heart, 00136 Rome, Italy
5
Department of Orthopedics and Rheumatological Sciences, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00136 Rome, Italy
6
Department of Life Sciences, Health, and Healthcare Professions, Link Campus University, 00165 Rome, Italy
*
Author to whom correspondence should be addressed.
Biomedicines 2024, 12(10), 2292; https://doi.org/10.3390/biomedicines12102292
Submission received: 25 June 2024 / Revised: 15 September 2024 / Accepted: 7 October 2024 / Published: 10 October 2024
(This article belongs to the Special Issue Advanced Research on Muscle and Bone Diseases)
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Abstract

Background: Osteoarthritis (OA) is the most common degenerative joint disease and affects millions of people worldwide, particularly the elderly population. The pathophysiology of OA is complex and involves multiple factors. Methods: Several studies have emphasized the crucial role of inflammation in this process. The receptor activator of NF-κB ligand (RANKL), the receptor activator of NF-κB (RANK), and osteoprotegerin (OPG) trigger a signaling cascade that leads to the excessive production of RANKL in the serum. Conclusions: The aim of this narrative review is (i) to assess the role of the RANK/RANKL/OPG signaling pathway in the context of OA progression, focusing especially on the physiopathology and on all the mechanisms leading to the activation of the inflammatory cascade, and (ii) to evaluate all the potential therapeutic strategies currently available that restore balance to bone formation and resorption, reducing structural abnormalities and relieving pain in patients with OA.
Keywords: osteoarthritis; joint disease; RANKL; OPG; targeted therapies; hyaluronic acid; denosumab osteoarthritis; joint disease; RANKL; OPG; targeted therapies; hyaluronic acid; denosumab

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MDPI and ACS Style

Di Cicco, G.; Marzano, E.; Mastrostefano, A.; Pitocco, D.; Castilho, R.S.; Zambelli, R.; Mascio, A.; Greco, T.; Cinelli, V.; Comisi, C.; et al. The Pathogenetic Role of RANK/RANKL/OPG Signaling in Osteoarthritis and Related Targeted Therapies. Biomedicines 2024, 12, 2292. https://doi.org/10.3390/biomedicines12102292

AMA Style

Di Cicco G, Marzano E, Mastrostefano A, Pitocco D, Castilho RS, Zambelli R, Mascio A, Greco T, Cinelli V, Comisi C, et al. The Pathogenetic Role of RANK/RANKL/OPG Signaling in Osteoarthritis and Related Targeted Therapies. Biomedicines. 2024; 12(10):2292. https://doi.org/10.3390/biomedicines12102292

Chicago/Turabian Style

Di Cicco, Gabriele, Emanuela Marzano, Andrea Mastrostefano, Dario Pitocco, Rodrigo Simões Castilho, Roberto Zambelli, Antonio Mascio, Tommaso Greco, Virginia Cinelli, Chiara Comisi, and et al. 2024. "The Pathogenetic Role of RANK/RANKL/OPG Signaling in Osteoarthritis and Related Targeted Therapies" Biomedicines 12, no. 10: 2292. https://doi.org/10.3390/biomedicines12102292

APA Style

Di Cicco, G., Marzano, E., Mastrostefano, A., Pitocco, D., Castilho, R. S., Zambelli, R., Mascio, A., Greco, T., Cinelli, V., Comisi, C., Maccauro, G., & Perisano, C. (2024). The Pathogenetic Role of RANK/RANKL/OPG Signaling in Osteoarthritis and Related Targeted Therapies. Biomedicines, 12(10), 2292. https://doi.org/10.3390/biomedicines12102292

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