Progranulin Knockout Accelerates Intervertebral Disc Degeneration in Aging Mice

• DOI: 10.1038/srep09102
• Publication Date: 2015-03-17T02:42:28Z
• Authors: Yun-peng Zhao; Qing-yun Tian; Ben Liu; Jason Cuellar; Brendon Richbourgh; Tang-hong Jia; Chuan-ju Liu
• Keywords: Mice, Knockout; 0303 health sciences; Age Factors; NF-kappa B; Gene Expression; Osteoclasts; Intervertebral Disc Degeneration; Immunohistochemistry; Article; Disease Models, Animal; Mice; 03 medical and health sciences; Cartilage; Progranulins; Osteogenesis; Disease Progression; Animals; Humans; Intercellular Signaling Peptides and Proteins; Bone Resorption; Intervertebral Disc; Genetic Association Studies; Granulins

AbstractIntervertebral 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.