Ten-m/Odz3 regulates migration and differentiation of chondrogenic ATDC5 cells via RhoA-mediated actin reorganization

J Cell Physiol. 2021 Apr;236(4):2906-2919. doi: 10.1002/jcp.30058. Epub 2020 Sep 22.

Abstract

Tenascin-like molecule major (Ten-m)/odd Oz (Odz), a type II transmembrane molecule, is well known to modulate neural development. We have reported that Ten-m/Odz3 is expressed in cartilaginous tissues and cells. Actin cytoskeleton and its regulator ras homolog gene family member A (RhoA) are closely associated with chondrogenesis. The present study aimed to evaluate the function and molecular mechanism of Ten-m/Odz3 during chondrogenesis, focusing on RhoA and the actin cytoskeleton. Ten-m/Odz3 was expressed in precartilaginous condensing mesenchyme in mouse limb buds. Ten-m/Odz3 knockdown in ATDC5 induced actin cytoskeleton reorganization and change of cell shape through modulation of RhoA activity and FGF2 expression. Ten-m/Odz3 knockdown suppressed ATDC5 migration and expression of genes associated with chondrogenesis, such as Sox9 and type II collagen, via RhoA. On the other hand, Ten-m/Odz3 knockdown inhibited proliferation of ATDC5 in a RhoA-independent manner. These findings suggest that Ten-m/Odz3 plays an important role in early chondrogenesis regulating RhoA-mediated actin reorganization.

Keywords: ATDC5; RhoA; Ten-m/Odz3; actin cytoskeleton; chondrogenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actin Cytoskeleton / drug effects
  • Actin Cytoskeleton / metabolism
  • Actins / metabolism
  • Animals
  • Cell Differentiation* / genetics
  • Cell Line
  • Cell Movement* / genetics
  • Cell Proliferation
  • Cell Shape
  • Chondrocytes / cytology*
  • Chondrocytes / metabolism*
  • Chondrogenesis* / genetics
  • Fibroblast Growth Factor 2 / metabolism
  • Gene Expression Regulation
  • Humans
  • Membrane Proteins / metabolism*
  • Mice
  • Mice, Inbred C57BL
  • Nerve Tissue Proteins / metabolism*
  • rhoA GTP-Binding Protein / metabolism*

Substances

  • Actins
  • Membrane Proteins
  • Nerve Tissue Proteins
  • TENM3 protein, human
  • Tenm3 protein, mouse
  • Fibroblast Growth Factor 2
  • rhoA GTP-Binding Protein