Open AccessLin28a overexpression reveals the role of Erk signaling in articular cartilage development
Author(s) -
Tatsuya Kobayashi,
Anastasia Kozlova
Publication year - 2018
Publication title -
development
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.754
H-Index - 325
eISSN - 1477-9129
pISSN - 0950-1991
DOI - 10.1242/dev.162594
Subject(s) - cartilage , microbiology and biotechnology , chondrocyte , mapk/erk pathway , biology , synovial joint , progenitor cell , signal transduction , embryonic stem cell , kinase , articular cartilage , anatomy , stem cell , pathology , osteoarthritis , medicine , genetics , alternative medicine , gene
Adult articular cartilage shows limited tissue turnover, and therefore development of the proper structure of articular cartilage is crucial for life-long joint function. However, the mechanism by which the articular cartilage structure is developmentally regulated is poorly understood. In this study, we show evidence that extracellular signal-regulated kinase (Erk) activation in articular chondrocyte progenitors during developmental stages control articular cartilage thickness. We found that overexpression of Lin28a, an RNA biding protein that regulates organismal growth and metabolism, in articular chondrocyte progenitor cells upregulated Erk signaling and increased articular cartilage thickness. Overexpression of a constitutively active Kras mimicked Lin28a overexpression, and inhibition of Erk signaling during embryonic stages normalized the cartilage phenotype of both Kras- and Lin28a-overexpressing mice. These results suggest that articular cartilage thickness is mainly determined during the process of embryonic synovial joint development which is positively regulated by Erk signaling.