Work

Impact of Wnt signals on human intervertebral disc cell regeneration

Year: 2018

Type: article

Abstract: Although preconditioning strategies are growing areas of interest for therapies targeting intervertebral discs (IVDs), it is unknown whether the Wnt signals previously implicated in chondrogenesis, Wnt3A, Wnt5A, and Wnt11, play key roles in the promotion of human nucleus pulposus (NP) cell redifferentiation. In this study, NP cells isolated from herniated disc patients were transduced with lentiviral vectors to overexpress the WNT3A, WNT5A, or WNT11 genes, or CRISPR associated protein 9 (Cas9)/single-guide RNA (sgRNA) vectors to knock out these genes. Following expansion, transduced NP cells were induced for redifferentiation toward the NP phenotype. The overexpression of specific WNT factors led to increases in both glycosaminoglycan (GAG) deposition and expression of redifferentiation genes. These effects were attenuated by knockout of the same WNT genes. These results indicate that specific WNT signals can regulate the expression of redifferentiation genes, unequally impact GAG deposition, and contribute to the redifferentiation of human NP cells. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:3196-3207, 2018.

Source: Journal of Orthopaedic Research®

DOI: 10.1002/jor.24115

Authors: Tyler Pizzute, Fan He, Xiao‐Bing Zhang, Ming Pei

Institutions: West Virginia University, West Virginia University Hospitals, Soochow University, Loma Linda University, State Key Laboratory of Experimental Hematology

Language: English

Topic: Spine and Intervertebral Disc Pathology

Subfield: Pathology and Forensic Medicine

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: bronze

Funders: Musculoskeletal Transplant Foundation, National Natural Science Foundation of China, National Institutes of Health, National Institute of Arthritis and Musculoskeletal and Skin Diseases