Effects of the Leptin-Mediated MAPK/ERK Signaling Pathway on Collagen II Expression in Knee Cartilage of Newborn Male Mice from Obese Maternal Offspring

• Published in: Biomolecules (Basel, Switzerland) Vol. 12; no. 3; p. 477
• Main Authors: Wang, Wenji, Zhang, Jialing, Huo, Yu, Zheng, Yuanzheng, Gui, Yonghao
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 21-03-2022; MDPI
• Subjects: Animals; Apoptosis; Arthritis; Cartilage; Cartilage - metabolism; Cartilage diseases; Cbfa-1 protein; Cells, Cultured; Chondrocytes; Collagen; Collagen (type II); Collagen - metabolism; collagen II; Diet; Disease; Epidemiology; Extracellular signal-regulated kinase; Females; Homeostasis; Intrauterine exposure; Kinases; Leptin; Leptin - metabolism; Male; MAP kinase; MAPK/ERK signaling pathway; Metalloproteinase; Mice; Mitogen-Activated Protein Kinases - metabolism; Molecular modelling; Neonates; obese maternal offspring; Obesity; Obesity - genetics; Obesity - metabolism; Offspring; Osteoarthritis; Overnutrition; Pregnancy; Protein kinase; Signal Transduction; Sox9 protein; Tissue inhibitor of metalloproteinase 1; Tissue Inhibitor of Metalloproteinase-1 - metabolism; Transcription factors; United States > US; China; MAPK/ERK signaling pathway; collagen II; leptin; obese maternal offspring; cartilage
• ISSN: 2218-273X; 2218-273X
• DOI: 10.3390/biom12030477

Epidemiological data suggest that various noncommunicable diseases develop as a result of altered maternal metabolic and physiological status due to exposure to several adverse factors during pregnancy. However, evidence for intrauterine exposure factors and mechanisms underlying the origin of early cartilage disease in chronic osteoarthritic disease is still lacking. In this study, we found that persistent overnutrition during pregnancy in obese mothers led to cartilage damage in neonatal male mice. This was mainly characterized by increased apoptosis with decreased expression of chondrocyte collagen II and low expression of Runx family transcription factor 2 (RUNX2) and SRY-box transcription factor 9 (SOX9). This reduction was also found to be associated with high leptin expression in newborn male mice of obese maternal offspring. Furthermore, the administration of leptin and mitogen-activated protein kinase (MAPK)-extracellular signal-regulated kinase (ERK) inhibitors in primary chondrocytes showed that leptin mediated MAPK/ERK signaling activation and thus affected the key regulators of cartilage matrix metallopeptidase 1 (MMP1) and tissue inhibitor of metalloproteinase 1 (TIMP1), thereby altering the expression of collagen II in mouse cartilage. Altogether, this study provided insights into the molecular mechanisms of cartilage-related disease development and also new clues and evidence for the fetogenetic origin of cartilage diseases.