TargetRx Atlas

MRNA basic information

  • mRNA ID:ENST00000327443
  • Gene Name:SP1
  • mRNA database:Ensembl
  • mRNA expression :up-regulated
  • mRNA Method:qRT-PCR
  • mRNA Pathway:SP1/TGFβR1/Smad2/SOX9 pathway
  • Evidence:validated
  • (mRNA-drug)

Drug basic information

  • Drug ID:DB01296
  • Drug Name:Glucosamine
  • Drug Method:up-regulated the gene expression

Disease basic infommation

  • Disease:fetal-originated osteoarthritis
  • Tissue:patients tissues

Other information

  • Title:Transforming growth factor-β receptor 1: An intervention target for genetic poor cartilage quality induced by prenatal dexamethasone exposure
  • Journal:Journal of Advanced Research
  • Published:2022
  • PubMed ID:35953031
  • Abstract:Introduction:Fetal-originated osteoarthritis is relative to poor cartilage quality and may exhibit transgenerational genetic effects. Previous findings revealed prenatal dexamethasone exposure (PDE) induced poor cartilage quality in offspring. Objectives:This study focused on further exploring molecular mechanism, heritability, and early intervention of fetal-originated osteoarthritis. Methods:Pregnant rats (F0) were segregated into control and PDE groups depending upon whether dexamethasone was administered on gestational days (GDs) 9-20. Some female offspring were bred with healthy males during postnatal week (PW) 8 to attain the F2 and F3 generations. The F3-generation rats were administrated with glucosamine intragastrically at PW12 for 6 weeks. The knee cartilages of male and female rats at different time points were harvested to assay their morphologies and functions. Furthermore, primary chondrocytes from the F3-generation rats were isolated to confirm the mechanism and intervention target of glucosamine. Results:Compared with the control, female and male rats in each generation of PDE group showed thinner cartilage thicknesses; shallower and uneven staining; fewer chondrocytes; higher Osteoarthritis Research Society International scores; and lower mRNA and protein expression of SP1, TGFβR1, Smad2, SOX9, ACAN and COL2A1. After F3-generation rats were treated with glucosamine, all of the above changes could be reversed. In primary chondrocytes isolated from the F3-generation rats of PDE group, glucosamine promoted SP1 expression and binding to TGFβR1 promoter to increase the expression of TGFβR1, p-Smad2, SOX9, ACAN and COL2A1, but these were prevented by SB431542 (a potent and selective inhibitor of TGFβR1). Conclusions:PDE induced chondrodysplasia in offspring and stably inherited in F3-generation rats, which was related to decreased expression of SP1/TGFβR1/Smad2/SOX9 pathway to reduce the cartilage matrix synthesis, without major sex-based variations. Glucosamine could alleviate the poor genetic cartilage quality in offspring induced by PDE by up-regulating SP1/TGFβR1 signaling, which was prevented by a TGFβR1 inhibitor. This study elucidated the molecular mechanism and therapeutic target (TGFβR1) of genetic chondrodysplasia caused by PDE, which provides a research basis for precisely treating fetal-originated osteoarthritis.
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