Abstract
Intervertebral disc (IVD) degeneration is a common degenerative disease, yet much is unknown about the mechanisms during its pathogenesis. Herein we investigated whether progranulin (PGRN), a chondroprotective growth factor, is associated with IVD degeneration. PGRN was detectable in both human and murine IVD. The levels of PGRN were upregulated in murine IVD tissue during aging process. Loss of PGRN resulted in an early onset of degenerative changes in the IVD tissue and altered expressions of the degeneration-associated molecules in the mouse IVD tissue. Moreover, PGRN knockout mice exhibited accelerated IVD matrix degeneration, abnormal bone formation and exaggerated bone resorption in vertebra with aging. The acceleration of IVD degeneration observed in PGRN null mice was probably due to the enhanced activation of NF-κB signaling and β-catenin signaling. Taken together, PGRN may play a critical role in homeostasis of IVD, and may serve as a potential molecular target for prevention and treatment of disc degenerative diseases.
Highlights
Intervertebral disc (IVD) degeneration is a common degenerative disease, yet much is unknown about the mechanisms during its pathogenesis
High-resolution analysis (Figure 1A, inserts) detected that in the cell clusters formed in all mentioned three parts of IVD tissue, PGRN was expressed in the extracellular matrix and cytoplasm of the cell clusters, which implied a role of PGRN during the process of IVD degeneration
We found new bone formation in the EP of PGRN2/2 mice as early as 4-month old, together with significantly higher levels of osteoblast marker genes, which indicated disorder of bone anabolism in IVD of these mice with aging
Summary
Intervertebral disc (IVD) degeneration is a common degenerative disease, yet much is unknown about the mechanisms during its pathogenesis. The levels of PGRN were upregulated in murine IVD tissue during aging process. PGRN may play a critical role in homeostasis of IVD, and may serve as a potential molecular target for prevention and treatment of disc degenerative diseases. PGRN is expressed in various cells and plays a critical role in many physiological and disease processes such as: wound healing[7], tumorigenesis[8] and inflammation[9,10,11]. We examined the expression pattern of PGRN in IVD tissue of human and mice under physiological and degenerative conditions, and determined the potential effects of PGRN deficiency on IVD degeneration as well as the alteration of signaling pathways during aging process
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
