The Effect of Nerve Growth Factor on Cartilage Fibrosis and Hypertrophy during In Vitro Chondrogenesis Using Induced Pluripotent Stem Cells
doi.org/10.15283/ijsc24097
- Author:
Se In JUNG
1
;
Si Hwa CHOI
;
Jang-Woon KIM
;
Jooyoung LIM
;
Yeri Alice RIM
;
Ji Hyeon JU
Author Information
1. Catholic iPSCs Research Center, CiSTEM Laboratory, Department of Medical Sciences, Graduate School The Catholic University of Korea, Seoul, Korea
- Publication Type:ORIGINAL ARTICLE
- From:International Journal of Stem Cells
2025;18(1):59-71
- CountryRepublic of Korea
- Language:English
-
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) pathway by NGF. In Conclusions, these findings provide valuable insights into the multifaceted role of NGF in cartilage hypertrophy and fibrosis, which might play a critical role in OA progression.
