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Impact of Wnt signals on human intervertebral disc cell regeneration
Author(s) -
Pizzute Tyler,
He Fan,
Zhang XiaoBing,
Pei Ming
Publication year - 2018
Publication title -
journal of orthopaedic research®
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.041
H-Index - 155
eISSN - 1554-527X
pISSN - 0736-0266
DOI - 10.1002/jor.24115
Subject(s) - wnt signaling pathway , wnt3a , microbiology and biotechnology , regeneration (biology) , chondrogenesis , biology , intervertebral disc , cell , gene , cancer research , stem cell , signal transduction , genetics , anatomy
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.