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The Effect of Nerve Growth Factor on Cartilage Fibrosis and Hypertrophy during In Vitro Chondrogenesis Using Induced Pluripotent Stem Cells

Se-In Jung, Si Hwa Choi, J. Kim, Jooyoung Lim, Yeri Alice Rim, Ji Hyeon Ju

International Journal of Stem Cells, 2024

5 citations

Abstract

Nerve growth factor (NGF) is a neurotrophic factor usually involved in the survival, differentiation, and growth of sensory neurons and nociceptive function. Yet, it has been suggested to play a role in the pathogenesis of osteoarthritis (OA). Previous studies suggested a possible relationship between NGF and OA; however, the underlying mechanisms remain unknown. Therefore, we investigated the impact of NGF in chondrogenesis using human induced pluripotent stem cells (hiPSCs)-derived chondrogenic pellets. To investigate how NGF affects the cartilage tissue, hiPSC-derived chondrogenic pellets were treated with NGF on day 3 of differentiation, expression of chondrogenic, hypertrophic, and fibrotic markers was confirmed. Also, inflammatory cytokine arrays were performed using the culture medium of the NGF treated chondrogenic pellets. As a result, NGF treatment decreased the expression of pro-chondrogenic markers by approximately 2∼4 times, and hypertrophic (pro-osteogenic) markers and fibrotic markers were increased by approximately 3-fold or more in the NGF-treated cartilaginous pellets. In addition, angiogenesis was upregulated by approximately 4-fold or more, bone formation by more than 2-fold, and matrix metalloproteinase induction by more than 2-fold. These inflammatory cytokine array were using the NGF-treated chondrogenic pellet cultured medium. Furthermore, it was confirmed by Western blot to be related to the induction of the glycogen synthase kinase-3 beta (GSK3β)…

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