title: C1q/TNF-related protein-3 exerts the chondroprotective effects in IL-1β-treated SW1353 cells by regulating the FGFR1 signaling.
abstract: Cartilage degeneration is known as a major cause of osteoarthritis (OA). C1q/TNF-related protein-3 (CTRP3) is an adipokine relative to chondrogenesis in vitro. However, its effect on cartilage degeneration in OA remains unclearly. In the present study, SW1353 cells were treated with IL-1β to imitate the microenvironment of OA for vitro research. Then, an obvious down-regulation of CTRP3 were validated in IL-1β-treated SW1353 cells. In addition, CTRP3 overexpression significantly attenuated the decrease in cell proliferation and increase in cell apoptosis triggered by IL-1β. Moreover, CTRP3 up-regulation significantly inhibited the expression of FGFR1, but with slight decrease in FGFR3 levels. Further analysis corroborated that FGFR1 overexpression markedly ameliorated the pro-proliferation and anti-apoptotic effects of CTRP3 elevation in cells upon IL-1β. Down-regulation of FGFR1 attenuated the increase in Ras-GTP expression caused by IL-1β stimulation. Moreover, EGFR1 elevation also abated the inhibitory effect of CTRP3 on Ras expression and the CRTP3-induced activation of PI3K/AKT in cells upon IL-1β. Furthermore, Ras inhibitor manumycin A antagonized the decrease in phosphorylation of PI3K and Akt caused by IL-1β treatment. Both Manumycin A and PI3K/Akt agonist FGF-1 attenuated the inhibitory effect of IL-1β on cell growth. Together, this research suggested that CTRP3 might protect chondrocytes against IL-1β-induced injury by suppressing the FGFR1- Ras/PI3K/Akt signaling-mediated growth inhibitory pathway, indicating a potential agent against osteoarthritis.
authors.affiliation: Department of Orthopedics, The First Affiliated Hospital of Xinxiang Medical University, Weihui, 453100, China. Electronic address: yuanxiahuangxx@163.com.
authors.forename: Yuanxia
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Department of Orthopedics, The First Affiliated Hospital of Xinxiang Medical University, Weihui, 453100, China.
authors.forename: Guang
authors.initials: G
authors.lastname: Wan
authors.affiliation: Department of Orthopedics, The First Affiliated Hospital of Xinxiang Medical University, Weihui, 453100, China.
authors.forename: Jingang
authors.initials: J
authors.lastname: Tao
mesh_terms: D045744:Cell Line, Tumor; D002813:Chondrosarcoma / Q000188:drug therapy*; D005786:Gene Expression Regulation / Q000187:drug effects; D020868:Gene Silencing; D006801:Humans; D053583:Interleukin-1beta / Q000494:pharmacology*; D010003:Osteoarthritis / Q000378:metabolism; D051496:Receptor, Fibroblast Growth Factor, Type 1 / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D048069:Tumor Necrosis Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: C506069:C1QTNF3 protein, human; D053583:Interleukin-1beta; D048069:Tumor Necrosis Factors; C496348:FGFR1 protein, human; D051496:Receptor, Fibroblast Growth Factor, Type 1
keywords: C1q/TNF-related protein-3; Cell injury; FGFR1; IL-1β; Osteoarthritis; Ras