Insights into the Notch signaling pathway in degenerative musculoskeletal disorders: Mechanisms and perspectives - 04/12/23

Doi : 10.1016/j.biopha.2023.115884

Gaoming Liu ^a,^{^{1
The authors contributed equally.}}, Jun Wei ^b,^{^{1
The authors contributed equally.}}, Wenfeng Xiao ^a,^c, Wenqing Xie ^a, Qin Ru ^d, Lin Chen ^d, Yuxiang Wu ^d,^⁎ , Ali Mobasheri ^e,^f,^g,^h,^i,^j,^⁎ , Yusheng Li ^a,^b,^⁎
^a Department of Orthopedics, Xiangya Hospital, Central South University, Changsha 410011, China
^b Department of Clinical Medical School, Xinjiang Medical University, Urumqi 830054, China
^c National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, 410011, China
^d Department of Health and Physical Education, Jianghan University, Wuhan 430056, China
^e Research Unit of Medical Imaging, Physics and Technology, Faculty of Medicine, University of Oulu, Oulu, Finland
^f Department of Regenerative Medicine, State Research Institute Centre for Innovative Medicine, Vilnius, Lithuania
^g Department of Orthopedics, University Medical Center Utrecht, Utrecht, the Netherlands
^h Department of Rheumatology and Clinical Immunology, University Medical Center Utrecht, Utrecht, the Netherlands
ⁱ Department of Joint Surgery, First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
^j World Health Organization Collaborating Center for Public Health Aspects of Musculoskeletal Health and Aging, Université de Liège, Liège, Belgium

^⁎Corresponding author.^⁎⁎Corresponding author at: Research Unit of Medical Imaging, Physics and Technology, Faculty of Medicine, University of Oulu, Oulu, Finland.Research Unit of Medical Imaging, Physics and Technology, Faculty of Medicine, University of OuluOuluFinland.^⁎⁎⁎Corresponding author at: Department of Orthopedics, Xiangya Hospital, Central South University, Changsha 410011, China.Department of Orthopedics, Xiangya Hospital, Central South UniversityChangsha410011China.

Abstract

Degenerative musculoskeletal disorders are a group of age-related diseases of the locomotive system that severely affects the patient's ability to work and cause adverse sequalae such as fractures and even death. The incidence and prevalence of degenerative musculoskeletal disorders is rising owing to the aging of the world’s population. The Notch signaling pathway, which is expressed in almost all organ systems, extensively regulates cell proliferation and differentiation as well as cellular fate. Notch signaling shows increased activity in degenerative musculoskeletal disorders and retards the progression of degeneration to some extent. The review focuses on four major degenerative musculoskeletal disorders (osteoarthritis, intervertebral disc degeneration, osteoporosis, and sarcopenia) and summarizes the pathophysiological functions of Notch signaling in these disorders, especially its role in stem/progenitor cells in each disorder. Finally, a conclusion will be presented to explore the research and application of the perspectives on Notch signaling in degenerative musculoskeletal disorders.

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Highlights

•	The Notch signaling pathway has a dual role in the progression of degenerative musculoskeletal disorders, which are progressively becoming a great social burden with the accelerating aging worldwide.
•	The primary physiological role of Notch signaling engenders the hypothesis that the senescent cells in these degenerative disorders are still “saving themselves” through reactivation of Notch signaling.
•	Many approaches or pathways can affect the expression of Notch signaling to maintain cell pool homeostasis, and conversely, regulating Notch signaling can treat or even reverse the development of degenerative musculoskeletal disorders.

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Keywords : Notch signaling pathway, Degenerative musculoskeletal disorders, Osteoarthritis, Osteoporosis, Sarcopenia, Intervertebral disc degeneration, Stem/progenitor cells