17β-estradiol activates SOX6 to balance the anabolism and catabolism via estrogen receptor 2 in chondrocyte.

Autor: Cao Y; Heilongjiang University of Chinese Medicine/ Internal Medicine Teaching and Research Section, The Second Affiliated Hospital of Heilongjiang University of Chinese Medicine, Harbin, China. 15765530806@163.com., Li Y; Heilongjiang University of Chinese Medicine/Department of Orthopedics and Traumatology, The Second Affiliated Hospital of Heilongjiang University of Chinese Medicine, Harbin, China. dayijingcheng1163@163.com., Yang X; Heilongjiang University of Chinese Medicine/Department of Orthopedics and Traumatology, The Second Affiliated Hospital of Heilongjiang University of Chinese Medicine, Harbin, China. panpan198804@163.com., Wang H; Heilongjiang University of Chinese Medicine/Department of Orthopedics and Traumatology, The Second Affiliated Hospital of Heilongjiang University of Chinese Medicine, Harbin, China. x19641206@163.com., Liu H; Heilongjiang University of Chinese Medicine/Department of Orthopedics and Traumatology, The Second Affiliated Hospital of Heilongjiang University of Chinese Medicine, Harbin, China. lhp1988528@163.com.
Jazyk: angličtina
Zdroj: Cellular and molecular biology (Noisy-le-Grand, France) [Cell Mol Biol (Noisy-le-grand)] 2024 May 27; Vol. 70 (5), pp. 132-138. Date of Electronic Publication: 2024 May 27.
DOI: 10.14715/cmb/2024.70.5.18
Abstrakt: We investigated the influence of 17β-estradiol (17β-E2) on cartilage extracellular matrix (ECM) homeostasis in postmenopausal women. We focused on the roles of estrogen receptors (ESR) and SOX6 in 17β-E2-mediated stimulation of ECM metabolism during chondrocyte (CH) degeneration. We compared the expression of anabolic genes (collagen II and aggrecan) and catabolic genes (MMPs and TIMPs) in IL-1β-induced CH degeneration in vitro, with and without 17β-E2 supplementation. We separately silenced the SOX6, ESR1, and ESR2 genes in CHs to determine their impact on 17β-E2 treatment. Additionally, we used Chromatin immunoprecipitation followed by DNA sequencing (ChIP-seq) and luciferase assays to investigate protein-DNA interactions within ESR2 and SOX6-promoter complexes. After three days of IL-1β treatment, ESR1/2, SOX6, collagen II, aggrecan, and TIMP1/3 were decreased, while MMP3/9/13 were increased. The addition of 17β-E2 partially reversed these effects, but silencing SOX6, ESR1, or ESR2 weakened the protective effects of 17β-E2. Silencing ESR2, but not ESR1, abolished the upregulation of SOX6 induced by 17β-E2. ESR2 was found to bind the SOX6 promoter and regulate SOX6 expression. 17β-E2 upregulates SOX6 through ESR2 mediation, and the synergistic effect of 17β-E2 and ESR2 on SOX6 balances ECM metabolism in CHs.
Databáze: MEDLINE