title: Progranulin knockout accelerates intervertebral disc degeneration in aging mice.
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.
authors.affiliation: 1] Department of Orthopaedic Surgery, New York University Medical Center, New York, NY. 10003 [2] Department of Spinal Surgery, Qilu Hospital, Shandong University, Jinan, Shandong 250012, PR China.
authors.forename: Yun-peng
authors.initials: YP
authors.lastname: Zhao
authors.affiliation: Department of Orthopaedic Surgery, New York University Medical Center, New York, NY. 10003.
authors.forename: Qing-yun
authors.initials: QY
authors.lastname: Tian
authors.affiliation: Department of Orthopaedic Surgery, New York University Medical Center, New York, NY. 10003.
authors.forename: Ben
authors.initials: B
authors.lastname: Liu
authors.affiliation: Department of Orthopaedic Surgery, New York University Medical Center, New York, NY. 10003.
authors.forename: Jason
authors.initials: J
authors.lastname: Cuellar
authors.affiliation: Department of Orthopaedic Surgery, New York University Medical Center, New York, NY. 10003.
authors.forename: Brendon
authors.initials: B
authors.lastname: Richbourgh
authors.affiliation: Department of Orthopaedic Surgery, Jinan Central Hospital, Shandong University, Jinan, Shandong 250012, PR China.
authors.forename: Tang-hong
authors.initials: TH
authors.lastname: Jia
authors.affiliation: 1] Department of Orthopaedic Surgery, New York University Medical Center, New York, NY. 10003 [2] Department of Cell Biology, New York University School of Medicine, New York, NY 10016.
authors.forename: Chuan-ju
authors.initials: CJ
authors.lastname: Liu
mesh_terms: D000367:Age Factors; D000818:Animals; D001862:Bone Resorption / Q000235:genetics; D002356:Cartilage / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D018450:Disease Progression; D015870:Gene Expression; D056726:Genetic Association Studies; D000077155:Granulins; D006801:Humans; D007150:Immunohistochemistry; D036341:Intercellular Signaling Peptides and Proteins / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism; D007403:Intervertebral Disc / Q000378:metabolism / Q000473:pathology; D055959:Intervertebral Disc Degeneration / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology*; D051379:Mice; D018345:Mice, Knockout; D016328:NF-kappa B / Q000378:metabolism; D010010:Osteoclasts / Q000378:metabolism; D010012:Osteogenesis / Q000235:genetics; D000077153:Progranulins; D015398:Signal Transduction; D013131:Spine / Q000378:metabolism / Q000473:pathology; D055114:X-Ray Microtomography; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism
chemical_list: D000077155:Granulins; C120204:Grn protein, mouse; D036341:Intercellular Signaling Peptides and Proteins; D016328:NF-kappa B; D000077153:Progranulins; D051176:beta Catenin